Abstract: Objective：To investigate the possible mechanism of Smac mimetic BV6 affecting the growth of human ovarian cancer SKOV3 cells by quantitative proteomics. Methods：MTT assay was used to detect the growth inhibition rate of SKOV3 cells treated with BV6 for 48 hours. Calculate the drug concentration at 50% inhibition rate as half the inhibitory concentration（IC50） and the subsequent experiments were performed at 0.05, 0.1, 0.2 μmol/L BV6. The control group and 0.05 μmol/L BV6 treatment group were observed under light microscope, after 48 h the cell morphology was changed. Application of isobarictags for relative and absolute quantitation (iTRAQ) techniques combined with Liquid Chromatography Tandem Mass Spectrometry to Screen Differential Protein Parallel Bioinformatics Analysis; Western blotting was used to detect the expression of caspase-3 in the control group and different concentrations of BV6. Results：BV6 can inhibit the proliferation of SKOV3 cells in a dose-dependent manner, and the variance analysis between groups and the comparison between any two groups were statistically significant (all P＜0.05). According to the formula, the IC50 of BV6 acting on SKOV3 cells for 48 h was 0.40 μmol/L. Based on FDR＜1%, 349 differential proteins were screened in the control group and 0.05 μmol/L BV6 for 48 h，251 were up-regulated and 98 down-regulated. Bioinformatics analysis showed differential protein and RNA transcription and protein. Translation, cell division and proliferation, apoptosis signal regulation and tumor angiogenesis were closely related. Western blotting showed that Caspase-3 protein expression was increased in the high, medium and low concentrations of BV6 for 48 h after treatment with SKOV3 cells. The expression of Caspase-3 protein was highest in the high concentration BV6 intervention group. Significance (all P＜0.05). Conclusions: BV6 promotes the death of SKOV3 cells by inhibiting RNA transcription, protein translation, cell division and proliferation, and tumor angiogenesis, and promoting the activation of Caspase-3 apoptosis.

Key words: Ovarian Neoplasms, Proteomics, Apoptosis, Caspases, Isotope labeling