Propofol enhances the lethality of cisplatin on liver cancer cells by up-regulating miR-195-5p

Abstract

Literatures have demonstrated that propofol can improve the efficacy of cisplatin, and miR-195 is implicated in the underlying mechanism concerning the anticancer effects of propofol. However, correlation between propofol and miR-195 has been little studied. This study clarified that propofol enhanced the inhibitory effect of cisplatin in liver cancer cells via miR-195-5p. 50 samples of liver cancer and para-cancer tissues in patients were collected and the difference in the expression of miR-195-5p was then analyzed. The liver cancer cells treated with gradient concentrations of cisplatin (3, 6.25, 12.5, 25, 50 μg/mL) and propofol (2, 5, 10 μg/mL) were tested for drug toxicity using CCK-8 assay. Next, following the transfection, the effects of propofol, cisplatin and miR-195-5p on the functions of liver cancer cells and the expressions of related proteins were analyzed by clone formation, flow cytometry and western blot. The downstream target genes of miR-195-5p were predicted by bio-informatics analysis and verified by dual-luciferase reporter assay, and their expressions in cancer cell was also calculated. The changes on the expressions of target genes were further detected by qRT-PCR and western blot. MiR-195-5p was lowly-expressed in liver cancer, and the up-regulation of miR-195-5p enhanced the sensitivity of liver cancer cells to cisplatin. Propofol inhibited the viability of liver cancer cells and stimulated the up-regulation of miR-195-5p. Propofol enhanced the lethality of cisplatin to liver cancer cells and reversed the repressive effects of miR-195-5p inhibitor on the efficacy of cisplatin. CCNE1 was the downstream target gene of miR-195-5p and its expression was up-regulated by miR-195-5p inhibitor in cisplatin-treated liver cancer cells. Collectively, propofol enhances the lethality of cisplatin to liver cancer cells by up-regulating miR-195-5p.