Synergistic Effect of miR-383 and Cisplatin on Inhibition of Growth, Proliferation, and Migration of Lung Cancer Cells.

Abstract

Background: Lung cancer (LC) is a common life-threatening malignancy in humans. Cisplatin has been widely used in the treatment of various types of cancer. miR-383 is dysregulated in multiple cancers, and participates in tumorigenic processes, including apoptosis, proliferation, metastasis, and drug resistance. This study aimed to investigate the synergistic effect of miR-383 and cisplatin in LC.

Methods: A549 cells were treated with cisplatin and miR-383 separately or in combination. Cell viability, apoptosis induction, stemness features, migratory capacity, and autophagy were measured by various methods. In addition, quantitative real-time PCR (qRT-PCR) was used to evaluate the expression levels of genes involved in apoptosis, stemness, and migration.

Results: The results demonstrated that miR-383 transfection in A549 cells increased their chemosensitivity to cisplatin, enhancing cisplatin-induced apoptosis (from 11.28% to 37.86%). This effect was mediated by regulating key genes such as Bcl-2 and Caspase-3 (P<0.0001). Moreover, the combination of miR-383 and cisplatin synergistically reduced cell migration and colony formation. It also downregulated metastatic and stemness-related genes, including MMP-2 and CD44, respectively (P<0.0001).

Conclusion: The findings indicate that the combination treatment of miR-383 and cisplatin suppressed cell proliferation, migration and colony formation while enhancing the sensitivity of A549 cells to chemotherapy compared to monotherapy. These results suggest that miR-383 combination therapy warrants further investigation as a potential strategy for LC treatment.