Synergism of ursolic acid and cisplatin promotes apoptosis and enhances growth inhibition of cervical cancer cells via suppressing NF-κB p65

OBJECTIVE: This study was designed to investigate the effect of combination of ursolic acid (UA) with cisplatin (DDP) on cervical cancer cell proliferation and apoptosis. METHODS: The mRNA and protein expressions of nuclear factor-kappa B (NF-κB) p65 in cervical cancer cells were examined using RT-PCR and western blot. MTT and colony formation assays were performed to examine the DDP toxicity and the proliferation ability of cervical cancer cells. Cell morphology was observed by means of Hoechst33258 and transmission electron microscopy (TEM). The apoptosis rate and cell cycle were assessed through flow cytometry assay. Western blot was used to detect the expression of apoptosis-related molecules. RESULTS: The mRNA and protein expressions of NF-κB p65 in cervical cancer cells were significantly higher than that in cervical epithelial cells. The combined treatment of UA and DDP inhibited cervical cancer cell growth and promoted apoptosis more effectively than DDP treatment or UA treatment alone (P < 0.05). Compared with the DDP group and UA group, the expressions of Bcl-2 and NF-κB p65 in DDP +UA group were decreased, while the expressions of Bax, Caspase-3 and PARP cleavage were observably increased. The expression of nuclear NF-κB p65 significantly reduced in UA group and DDP +UA group. si-p65 group displayed a decrease of cell proliferation ability and led to a significant reduction in the number of SiHa cell colony formation. CONCLUSION: The combination of UA with DDP could more effectively inhibit SiHa cells proliferation and facilitate cell apoptosis through suppressing NF-κB p65.