Schedule-dependent effects of sorafenib in combination with paclitaxel on human hepatocellular carcinoma cell line BEL-7402

Abstract

Sorafenib is a multi-targeted antitumor drug. The monotherapy efficacy of sorafenib is relatively low. This study was to evaluate the schedule-dependent effect of sorafenib in combination with paclitaxel (TAX) on human hepatocellular carcinoma cell BEL-7402, and explore the underlying mechanism. BEL-7402 cells were treated with sorafenib or paclitaxel alone or in three different schedules: sorafenib was give prior to, after, or simultaneously with paclitaxel. The half maximal inhibitory concentration (IC50) of sorafenib and paclitaxel was estimated by MTT. Alteration of cell cycle and apoptosis were analyzed by flow cytometry. The protein level of Bcl-2 in BEL-7402 cells was measured by western blot. At 48 h, the IC50 of sorafenib and paclitaxel for BEL-7402 cells was (2.43+/-0.32) microg/mL and (1.89+/-0.72) microg/mL, respectively. Sorafenib caused cell cycle arrest at S phase, while paclitaxel blocked cells at G2/M phase. S and G2/M phases were extended and a higher apoptotic rate (36.43+/-2.29)% was induced when sorafenib was given after paclitaxel in comparision with other groups (P<0.01). The protein level of Bcl-2 was the lowest in BEL-7402 cells treated with sorafenib after paclitaxel. Administration of sorafenib after paclitaxel induces a higher apoptotic rate in BEL-7402 cells than administration before or simutanously with paclitaxel. This is probably due to that the two drugs act on different cell cycle phases and the expression of Bcl-2 might be involved.