Anlotinib Inhibits Cisplatin Resistance in Non-Small-Cell Lung Cancer Cells by Inhibiting MCL-1 Expression via
Lile Wang1,2, Lu Xu1,2, Shuhua Han1,2
1Department of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
Background:
Anlotinib is an effective targeted therapy for advanced non-small-cell lung cancer (NSCLC) and has been found to mediate chemoresistance in many cancers. However, the underlying molecular mechanism of anlotinib mediates cisplatin (DDP) resistance in NSCLC remains unclear.
Methods:
Cell viability was assessed by the cell counting kit 8 assay. Cell proliferation, migration, and invasion were determined using the colony formation assay and transwell assay. The mRNA expression levels of mesenchymal-epithelial transition factor (MET) and myeloid cell leukemia-1 (MCL-1) were measured by quantitative real-time PCR. Protein expression levels of MET, MCL-1, and STAT3/Akt pathway-related markers were examined using western blot analysis.
Results:
Our data showed that anlotinib inhibited the DDP resistance of NSCLC cells by regulating cell proliferation and metastasis. Moreover, MET and MCL-1 expression could be decreased by anlotinib treatment. Silencing of MET suppressed the activity of the STAT3/Akt pathway and MCL-1 expression. Furthermore, MET overexpression reversed the inhibitory effect of anlotinib on the DDP resistance of NSCLC cells, and this effect could be eliminated by MCL-1 knockdown or ACT001 (an inhibitor for STAT3/Akt pathway).
Conclusion:
Our results confirmed that anlotinib inhibited DDP resistance in NSCLC cells, which might decrease MCL-1 expression via mediating the MET/STAT3/Akt pathway.
Insights
Anlotinib combats cisplatin resistance in non-small-cell lung cancer (NSCLC) by reducing MET and MCL-1 expression. This targeted therapy impacts the MET/STAT3/Akt pathway, offering new insights for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Anlotinib is a targeted therapy for advanced non-small-cell lung cancer (NSCLC).
- Anlotinib's role in mediating chemoresistance is known, but its mechanism in cisplatin-resistant NSCLC is unclear.
Purpose of the Study:
- To elucidate the molecular mechanism by which anlotinib mediates cisplatin (DDP) resistance in NSCLC.
- To investigate the role of the MET/STAT3/Akt pathway in anlotinib's effects on DDP resistance.
Main Methods:
- Cell viability, proliferation, migration, and invasion assays were performed.
- Quantitative real-time PCR and western blot analysis were used to measure MET, MCL-1, and STAT3/Akt pathway markers.
Main Results:
- Anlotinib inhibited DDP resistance in NSCLC cells by regulating proliferation and metastasis.
- Anlotinib treatment decreased MET and MCL-1 expression, suppressing the STAT3/Akt pathway.
- MET overexpression reversed anlotinib's effect, which was overcome by MCL-1 knockdown or STAT3/Akt pathway inhibition.
Conclusions:
- Anlotinib inhibits DDP resistance in NSCLC cells.
- This effect is mediated by decreased MCL-1 expression through the MET/STAT3/Akt pathway.
More Related Videos
Related Concept Videos
lncRNA - Long Non-coding RNAs
PI3K/mTOR/AKT Signaling Pathway
Targeted Cancer Therapies
There are several types of targeted therapies against...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
The Intrinsic Apoptotic Pathway
Inhibition of Cdk Activity


