The natural interaction between gambogic acid and oxaliplatin and its probably mechanism

Objective:To assess the natural interaction between gambogic acid and oxaliplatin widely used in gastrointestinal cancer treatment,and to investigate the influence of gambogic acid on cell apoptosis and drug-associated gene expression. Methods:Synergistic interaction on human gastric cancer cell lines BGC-823 and MKN-28 was evaluated using the combination index (CI) method. The double staining with both Annexin-Ⅴ-FITC and PI was employed to distinguish the apoptotic cells from others. Expression of drug- associated genes,i.e.,excision repair cross-complementing(ERCC1),breast cancer susceptibility gene 1(BRCA1) of BGC-823 with or without gambogic acid treatment were measured by real-time quantitative RT-PCR. Results:Gambogic acid had a synergistic effect on the cytotoxicity of oxaliplatin in BGC-823 cells. The combination of gambogic acid and oxaliplatin could also induce apoptosis in a synergistic manner. Most prominently,ERCC1,BRCA1 mRNA levels of BGC-823 were markedly suppressed at 0.070-,and 0.140-fold respectively by the presentation of gambogic acid. Conclusion:Gambogic acid appears a promising candidate for combining with oxaliplatin in cancer chemotherapy treatment. The possible synergistic mechanisms maybe the synergistic apoptotic effect and the downregulation of drug-associated genes.