Antitumor activity of gambogic acid lysinate in human SiHa cells in vitro and in vivo
Abstract Background: Cervical cancer is a major cause of death for women worldwide and human papillomavirus (HPV) infection is the main cause of cervical cancer. The purpose of this study was to explore the anti-tumor activity of gambogic acid lysinate and clarify its mechanism in SiHa cells. Methods: In the present study, cell viability was detected by means of an MTT assay, a cell growth curve was drawn with Microsoft Excel 2010, the cell cycle and cell apoptosis were evaluated by flow cytometry, Western blotting was employed to explore the mechanism of gambogic acid lysinate, and caspase-3 activity was determined with a colorimetric Caspase-3 assay kit. Additionally, the in vivo antitumor activity of gambogic acid lysinate was studied through a xenograft tumor model established with nude mice. Results: The results showed that gambogic acid lysinate inhibited the proliferation of both SiHa cells (half-maximal inhibitory concentration (IC50) values: 0.83 μmol/l and 0.77 μmol/l for 48 h and 72 h) and HeLa cells (IC50 >2 μmol/l). In SiHa cells, gambogic acid lysinate (1 and 2 μmol/l) inhibited cell proliferation and 2 μmol/l gambogic acid lysinate induced cell apoptosis and decreased the number of S phase cells. Both 1 and 2 μmol/l gambogic acid lysinate increased the number of G0/G1 phase cells. The results of a Western blot assay demonstrated that P53 and P21 were involved in SiHa cell G0/G1 phase arrest and that Bcl-2 and BAX were involved in SiHa cell apoptosis. An in vivo study showed that the growth of SiHa cell xenograft tumors was inhibited by gambogic acid lysinate (2.5 mg/kg body weight), however, gambogic acid lysinate (2.5 mg/kg body weight) had no significant effect on mouse weight gain. Conclusions: gambogic acid lysinate is a promising candidate for cervical cancer therapy.