Effects Of Sorafenib On Proliferation And Apoptosis Of Human Ovarian Cancer Cell Line SKOV-3

Objective This study was to evaluate the effect of sorafenib alone or in combinationwith paclitaxel on human ovarian cancer cell SKOV-3.Methods MTT was used to examine the effects of sorafenib at differentconcentrations (1.5,3.0,6.0,12.0and24.0μmol/L) and different time points (24,48and72h) on proliferation of SKOV-3cells. Hoechst33258staining assay was used to observesorafenib-induced morphological changes; SKOV-3cells were treated with sorafenib orpaclitaxel alone or in three different schedules: sorafenib was given prior to, after orsimultaneously with paclitaxel. Alteration of cell cycle and apoptosis were analyzed byflow cytometry.Results The results indicated that sorafenib could induce apoptosis of SKOV-3cellsand the apoptotic rate was increased with the increase of sorafenib concentration comparedwith the control group (P<0.05). Apoptosis occurred when SKOV-3cells were incubatedwith sorafenib, evidenced by morphological changes and increased proportion of hoechstpositive cells. Sorafenib caused cell cycle arrest at S phase while paclitaxel blocked cells atG2-M phase. S and G2-M phases were extended and a higher apoptotic rate was inducedwhen sorafenib was given after paclitaxel (P<0.05).Conclusions Sorafenib can effectively inhibit the proliferation of SKOV-3cells intime and dose dependent manners; Sorafenib can induce apoptosis of SKOV-3cells;Administration of sorafenib after paclitaxel induces a higher apoptotic rate in SKOV-3cells than administration before or simutanously with paclitaxel. This is probably due tothat the two drugs act on different cell cycle phases.