Anticancer effect of combinational therapy (sorafenib and anti-miR-222) on renal cell carcinoma cell lines: an invitro study

Abstract

Background: Sorafenib chemotherapy drug can fight renal cell carcinoma (RCC) cells, the most common kidney cancer, by preventing cell migration and viability and stimulating apoptosis. In recent years, studies on combination therapies in cancer have increased due to greater effectiveness and prevention of drug resistance. In this study, we aimed to investigate the apoptotic and anti-metastatic effect of sorafenib and anti-miR-222 on RCC cell lines Methods: 786-O and Caki-1 were used as RCC cell lines. Gene expression of PD-L1, Bim, miR-34a, miR-122, miR-513, and miR-570 were evaluated using quantitative real-time polymerase chain reaction(qRT-PCR) before and after sorafenib treatment. Changes in cell viability, apoptosis, and cell migration respectively were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, flow cytometry, and scratch assay after treatment of 786-O and Caki-1 cell lines with sorafenib and anti-miR-222. Results: Sorafenib led to increased expression of PD-L1, Bim, miR-34a, miR-122, miR-513, and miR-570genes in 786-O and Caki-1 cell lines. MTT assay results showed that cotreatment of 786-O and Caki-1 cell lines with sorafenib and anti-miR-222 solely and together decrease cell viability but combination therapies results were more significant. Also, the data of the apoptosis test showed an increased apoptosis rate in both 786-O and Caki-1 cell lines after treatment with sorafenib and anti-miR-222 solely and together but combination therapies results were more remarkable. The scratch test results also showed a decrease in cell migration in both cell lines in the treatment with sorafenib and anti-miR-222 solely and together after 24 and 48 hours but combination therapies results were more considerable. Conclusion: Therefore, the present study shows a significant enhancement of the increase in apoptosis, as well as a significant decrease in cell migration and viability, after the use of sorafenib and anti-miR-222 at the same time. It seems that these results can contribute to the development of therapeutic strategies against RCC.