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PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These findings underscore the significance of ncRNAs in autophagy regulation and drug resistance.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Targeting specific ncRNAs that control autophagy pathways may represent a promising strategy for enhancing GIST therapy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Growing evidence suggests that ncRNAs, particularly miRNAs and lncRNAs, play crucial roles in regulating ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In tumor cells, ncRNAs influence ferroptosis by modulating genes involved in iron metabolism, antioxidant defense, and membrane lipid composition.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For example, miRNAs have been shown to regulate ferroptosis by targeting key genes such as GPX4, FTH1, and SLC7A11, thereby affecting tumor cell survival .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In gastrointestinal cancers, including gastric and colorectal cancer, miRNAs regulate ferroptosis by modulating iron homeostasis, lipid peroxidation, and oxidative stress responses .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
miRNAs regulate ferroptosis by binding to target genes' 3' untranslated regions (3'UTRs), influencing iron balance and redox homeostasis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For instance, miR-27a downregulates GPX4, a critical antioxidant enzyme suppressing lipid peroxidation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Reduced GPX4 expression enhances ferroptosis and alters tumor cell proliferation and viability .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Similarly, miR-9 targets SLC7A11, a key component of system Xc, thereby decreasing intracellular glutathione (GSH) levels and increasing oxidative stress and iron accumulation .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These findings highlight the importance of miRNAs in regulating ferroptosis through direct control of iron metabolism and antioxidant capacity.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
lncRNAs have also emerged as important regulators of ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Unlike miRNAs, lncRNAs typically modulate gene expression by interacting with transcription factors or epigenetic regulators.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
lncRNA H19, for example, is upregulated in several cancers and influences ferroptosis by targeting miR-675 and regulating iron metabolism genes .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Another lncRNA, p53RRA, enhances p53 transcriptional activity, suppresses GPX4 expression, and promotes ferroptosis .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These mechanisms suggest that lncRNAs regulate ferroptosis by controlling oxidative stress and iron-related gene expression.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
circRNAs, a newly identified ncRNA subtype, regulate ferroptosis primarily through miRNA sponging.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In gastric cancer, circ_0000284 binds to miR-29a, reducing its activity.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Since miR-29a inhibits FTH1, a ferroptosis suppressor, this sponging effect enhances ferroptosis .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Conversely, circRNA CDR1as regulates miR-7 and upregulates FTH1 expression, suppressing ferroptosis and promoting tumor growth and drug resistance .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These studies illustrate the dual roles of circRNAs in modulating ferroptosis, either enhancing or inhibiting the process through miRNA regulation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Targeting ncRNAs presents a promising therapeutic strategy for modulating ferroptosis in cancer.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
RNA interference and CRISPR/Cas9 technologies have enabled precise manipulation of specific miRNAs and lncRNAs, allowing selective ferroptosis induction in tumor cells.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For example, miRNA mimics or inhibitors can regulate ferroptosis-related genes involved in iron metabolism.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
CRISPR-based approaches offer high specificity and the potential to fine-tune ferroptosis activation without damaging normal cells .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These strategies not only improve treatment efficacy but may also enhance anti-tumor immunity.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Overall, ncRNA-based modulation of ferroptosis opens up new avenues for precision cancer therapy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
PCD plays a vital role in preventing uncontrolled proliferation and malignant transformation, while its dysregulation is commonly associated with tumor progression and therapeutic resistance.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
IM has been shown to induce autophagy, apoptosis, and ferroptosis as a first-line treatment for GIST.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The crosstalk among these PCD pathways significantly influences drug sensitivity and is closely linked to metastasis and recurrence.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This study systematically explored the regulatory roles of ncRNAs in PCD pathways in GIST, highlighting their key mechanisms in apoptosis, autophagy, and ferroptosis and their potential association with malignancy and drug resistance, thereby providing a theoretical foundation for precision therapy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
However, challenges remain in understanding the interactions among different ncRNAs, their roles within the tumor immune microenvironment, and developing efficient and targeted delivery strategies.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Future research integrating single-cell sequencing, multi-omics analysis, and functional validation is expected to further elucidate the ncRNA-PCD-GIST regulatory axis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In the next few years, key directions include network-level dissection of ncRNA-PCD regulation, clinical translation of ncRNA biomarkers, development of therapeutic strategies such as ASOs and CRISPR tools, and integration of ncRNA targeting with immunotherapy to optimize treatment paradigms.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Despite the comprehensive analysis of ncRNA-mediated PCD regulation in GIST, several limitations should be acknowledged.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The study is largely based on literature synthesis and existing experimental data, lacking in vivo and in vitro validation of specific ncRNAs, making it difficult to define their direct functional roles in PCD.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Given the molecular heterogeneity of GIST, ncRNA expression and function may vary across different mutation subtypes, which were not fully addressed here.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Moreover, although we discussed ncRNAs as potential therapeutic targets, current ncRNA-based interventions in GIST remain in the early stages.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Efficient delivery, stability, and off-target minimization remain major barriers to clinical application.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Notably, the role of ncRNAs in shaping the immune microenvironment of GIST is not well understood, although PCD pathways are increasingly recognized to intersect with tumor immune regulation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Future work should combine single-cell sequencing, integrative multi-omics, and functional studies to systematically unravel the molecular landscape of the ncRNA-PCD-GIST axis and identify critical regulators involved in tumor progression, immune modulation, and drug resistance.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Exploration of additional cell death pathways in GIST may expand the therapeutic target pool and contribute to developing a more comprehensive risk stratification model.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Such a model could incorporate conventional biological features and PCD-related molecular profiles to support more precise clinical decision-making.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Identifying novel PCD-associated prognostic or predictive biomarkers and elucidating their mechanistic roles may accelerate the advancement of personalized therapy in GIST.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
However, up to 40–50% of GISTs develop secondary resistance after an average of 24 months of imatinib treatment.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
It has been reported that autophagy can promote the survival of GIST cells and induce drug resistance.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Presently, the specific mechanism of autophagy in GISTs with imatinib resistance is not clear.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The cell-counting kit (CCK)-8 method and flow cytometry were used for in vitro drug sensitivity testing and autophagy level detection.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Detection of the apoptosis level was by flow cytometry with the annexin V Kit.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Western blotting was used to analyze the role of autophagy and apoptosis in GIST cells with CQ alone, imatinib alone, or in combination, and to analyze MAPK pathway expression.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
In vitro results were confirmed by in vivo experiments using the mice model.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Hematoxylin and eosin and immunohistochemical staining were used to detect the pathological characteristics and immunophenotype of the transplanted tumor.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Detection of KIT and PDGFRA gene mutations in the transplanted imatinib-resistant GIST was done by denaturing high performance liquid chromatography (DHPLC) and direct sequencing.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
ERK and KIT expression and regulation levels were detected by Western blotting.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
In vitro and vivo experiments, the autophagy level of imatinib-resistant cells was higher than that of normal cells; CQ combined with imatinib can promote apoptosis by blocking autophagy of imatinib-resistant cells.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
In the meanwhile, we found that the phosphorylation level of ERK may be related to autophagy.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Our data suggest that autophagy through the MAPK/ERK pathway may play a pivotal role in imatinib-resistant GIST proliferation.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Moreover, combining an autophagy inhibitor with imatinib may be a potential valuable strategy in overcoming acquired resistance in GIST patients.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, accounting for 1–3% of all digestive tract tumors and almost 5% of all soft tissue sarcomas.1 With the increase in knowledge and improvement of the level of diagnosis, the incidence of GISTs is increasing year by year.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Up to 85% of GISTs acquire mutations in the KIT gene and 3–18% in the platelet-derived growth factor receptor A (PDGFRA) gene.2 GIST responds to treatment with targeted KIT/PDGFRA inhibitors such as imatinib mesylate.3–5 However, up to 40–50% of GISTs develop secondary resistance after an average of 24 months of imatinib treatment.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Based on the natural evolution of the disease, the patient could be placed on a higher dose of imatinib or a tyrosine kinase inhibitor such as ripretinib, though resistance can be a challenge.6–8 Resistance to imatinib has been of great interest in recent research.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Autophagy and apoptosis are crucial and fundamental to cancer development.9 It has been reported that autophagy can promote the survival of GIST cells and induce drug resistance.10,11 Moreover, a combination of autophagy inhibitors and imatinib has achieved almost complete remission in the treatment of imatinib-resistant chronic myeloid leukemia.12,13 Inhibition of autophagy synergizes with imatinib to increase GIST cell death and retard the outgrowth of residual GIST viable cells when compared with imatinib alone therapy.14 Combining imatinib and autophagy inhibition is a potentially valuable strategy to promote GIST cytotoxicity and to diminish both cellular quiescence and acquired resistance in GIST patients.15 Presently, the specific mechanism of autophagy in GISTs with imatinib resistance is not clear.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The PI3K/Akt/mTOR and Mitogen Activated Protein Kinase (MAPK) pathways are pivotal for cell growth and differentiation and are frequently hyperactivated during tumorigenesis (Figure 1E).16 MAPK signaling plays a critical role in the balance of apoptosis and autophagy in the response to chemotherapeutic agents.17 Activated MAPK can transmit extracellular signals to regulate cell growth, proliferation, differentiation, migration, apoptosis, etc.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Apoptosis and macroautophagy (hereafter referred to as autophagy) can be induced by extracellular stimuli such as treatment with chemotherapeutic agents, resulting in different cell responses to these drugs.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Figure 1(A) Effect of imatinib on drug sensitivity of GIST882 cell line. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Effect of imatinib on drug sensitivity of GIST882-ir cell line. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Effect of imatinib and chloroquine on apoptosis of GIST882-ir cell line (after 48h). (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The effects of Imatinib and Chloroquine on cell viability of GIST882-ir strains after 8h, 24h and 48h. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The two essential proliferative intracellular signaling pathways, PI3K/Akt/mTOR and MAPK. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Five group Western blot results.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
1.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882, 2.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882-ir, 3.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882-ir +im, 4.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882-ir +CQ, 5.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882-ir +im+CQ. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Effect of imatinib on drug sensitivity of GIST882 cell line. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Effect of imatinib on drug sensitivity of GIST882-ir cell line. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Effect of imatinib and chloroquine on apoptosis of GIST882-ir cell line (after 48h). (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The effects of Imatinib and Chloroquine on cell viability of GIST882-ir strains after 8h, 24h and 48h. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The two essential proliferative intracellular signaling pathways, PI3K/Akt/mTOR and MAPK. (
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Five group Western blot results.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
1.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882, 2.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882-ir, 3.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882-ir +im, 4.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882-ir +CQ, 5.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882-ir +im+CQ.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Our previous research suggests the possibility of activation of the RAS-RAF-MEK-ERK pathways driven by a KIT-independent oncogenic mechanism in GISTs.18 In imatinib-resistant GISTs with both KIT V559D and BRAF V600E mutations, the inhibition of KIT V559D by imatinib caused a strong decrease of AKT phosphorylation, while ERK1/2 phosphorylation was not affected.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The detection of alterations in the MAPK pathway in GISTs would be innovative and could be relevant in receptor tyrosine kinase inhibitor resistance or autophagy.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Herein, we explored the role of an autophagy inhibitor, chloroquine (CQ) in imatinib-resistant GISTs and elaborated the role of the MAPK/ERK pathway in autophagy inhibition.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882 cell lines, GIST882 imatinib-resistant cell lines, GIST882 cell mice, GIST imatinib-resistant cell mice.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
GIST882: normal control group; GIST882-ir: imatinib-resistant cell lines; GIST882-ir +im: imatinib-resistant cell lines + imatinib; GIST882-ir +CQ: imatinib-resistant cell lines + chloroquine; GIST882-ir +im+ CQ: imatinib-resistant cell lines + imatinib + chloroquine.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The above imatinib-resistant cell lines and GIST882 were inoculated into nude mice to observe their tumorigenicity.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The tumor size, growth rate, and survival time of nude mice were observed.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
Forty 4–5 weeks old, 16–18 g, and specific pathogen-free NOD/SCID male mice were purchased from the Shanghai Slyke Laboratory Animal Limited Liability Company (license number: SCXK (Shanghai) 2013–0018, certification number: 0301907).
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The quality of drinking water was in accordance with the national standard of the People’s Republic of China (GB5749-2006).
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The license number of the laboratory animal room was SYXK (zhejiang) 2015–0008.
PMC7342409
Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway
The temperature and relative humidity of the feeding environment ranged from 20–25 °C and 40–70%, respectively.