Scutellarin Enhances Carboplatin-induced Cytotoxicity Against Ovarian Cancer by Decrease the Expression of TRIM32

OBJECTIVE To investigate the adjuvant effect and mechanisms of scutellarin in carboplatin-based chemotherapy on ovarian cancer. METHODS CCK-8 assay was performed to evaluate the effect of scutellarin and different concentrations of carboplatin on changing the viability of A2780 ovarian cancer cells. Western blotting analysis was performed to detect the effect of scutellarin and carboplatin on changing the expression of TRIM32 and Bcl-2 and activation of caspase-9 and caspase-3 in A2780 cells. Flow cytometry analysis was performed to detect the reactive oxygen species(ROS) level, mitochondrial membrane potential and apoptotic rate of A2780 cells. RESULTS Adjuvant therapy of scutellarin significantly decreased the IC₅₀ of carboplatin to A2780 cells. Scutellarin obviously inhibited the expression of TRIM32 in A2780 cells. However, transfection with TRIM32 plasmid suppressed the effect of scutellarin on enhancing the cytotoxicity of carboplatin against ovarian cancer. Scutellarin decreased the expression of Bcl-2 and promoted the carboplatin-induced generation of ROS. Combination with carboplatin and scutellarin significantly induced the collapse of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and occurrence of cell apoptosis in A2780 cells. However, transfection with TRIM32 plasmid obviously suppressed the mitochondrial apoptosis pathway induced by the combination treatment with scutellarin and carboplatin in the A2780 cells. CONCLUSION Scutellarin decrease the expression of TRIM32 and thus enhance the carboplatin-induced mitochondrial apoptosis in ovarian cancer.