Cepharanthine hydrochloride reverses P-glycoprotein-mediated multidrug resistance in human ovarian carcinoma A2780/Taxol cells by inhibiting the PI3K/Akt signaling pathway

Abstract

Ovarian cancer has the highest mortality rate among gynecologic malignant tumors. The major obstacle to treatment success is multidrug resistance (MDR) to chemotherapy drugs. Cepharanthine hydrochloride (CH), a natural alkaloidderived compound, has shown MDR reversal potency in several tumor cell lines; however, the molecular mechanism is not entirely known. In the present study, we assessed whether CH sensitized malignant cells to chemotherapy drugs in ovarian cancer and explored the relevant mechanism. We found that CH reduced the IC50 value of paclitaxel and increased intracellular rhodamine-123 accumulation in human ovarian cancer A2780/Taxol cells in a concentration-dependent manner. Reverse transcription polymerase chain reaction and western blot assay demonstrated that CH inhibited MDR1 expression as indicated by reduced mRNA and protein levels in A2780/ Taxol cells. In addition, the inhibitory effect was strengthened after CH was combined with the specific PI3K/Akt signaling pathway inhibitor LY294002. Furthermore, p-Akt expression decreased gradually with the concentration of CH (2, 4 and 8 μM). Taken together, these findings indicated that CH reversed P-glycoprotein-mediated MDR in A2780/Taxol cells by inhibiting the PI3K/Akt signaling pathway.