Objective: To study the effect of beta-hydroxyisovaleryl shikonin (beta-HIVS) combined cisplatin on activities of ovarian cancer cell line SKOV3 in vivo and its possible mechanisms.
Methods: Cells were divided into the blank control group and six beta-HIVS groups (2 - 30 micromol/L). Effect of beta-HIVS at different concentrations on the activities of ovarian cancer cell line SKOV3 was detected using MTT assay. SKOV3 cells were treated with cisplatin (10, 20, and 40 micromol/L) and beta-HIVS (0.25, 1, and 2.5 micromol/L) combined cisplatin. Effect of beta-HIVS combined cisplatin on the activities of ovarian cancer cell line SKOV3 was determined by MTT assay. The expression of Bcl-2 and Bax after treated by different concentrations of beta-HIVS was detected by Western blot.
Results: The activities of SKOV3 were inhibited by different concentrations of beta-HIVS dose-dependently. The 50% inhibition rate (IC50) was 7.37 micromol/L. There was statistical difference in IC50 between each concentration beta-HIVS group and the blank control group (P < 0.05). There was statistical difference in IC50 between the beta-HIVS (1 and 2.5 micromol/L) combined cisplatin groups and the cisplatin group (P < 0.05, P < 0.01). The synergistic effect on beta-HIVS showed dose-dependent manner. Results of Western blot showed beta-HIVS at different concentrations (5, 7.5, and 10 micromol/L) could obviously up-regulate the expression level of Bax protein and inhibit the expression level of Bcl-2 protein, showing statistical difference when compared with the control group (P < 0.01). CONCLUSIONS; HIVS could obviously inhibit in vitro growth of SKOV3 in a dose-dependent manner. With the range of concentration, beta-HIVS showed synergetic effect with cisplatin. Besides, along with increasing beta-HIVS concentrations, the synergetic effect was more significant. The synergetic effect might accelerate the apoptosis of SKOV3 through up-regulating Bax expression and inhibiting Bcl-2 expression.