Gambogic acid (GA), the main active component of gamboge, is well known for its marked antitumor effect in vitro and in vivo. The aim of this study was to assess the natural interaction between GA and chemotherapeutic agents,
5-fluorouracil (5-FU),
oxaliplatin (Oxa), and
docetaxel (Doc), which are widely used in
gastric cancer treatment. This study also investigated the effect of GA on cell apoptosis and
drug-associated gene expression for further mechanism research. Synergistic interaction on human
gastric cancer BGC-823 cells and MKN-28 cells was evaluated using the combination index (CI) method. The double staining method with
Annexin-V-FITC and PI was employed to distinguish the apoptotic cells from others. Expression of
drug-associated genes, that is,
thymidylate synthase (TS), excision repair cross-complementing (ERCC1), BRCA1, tau, and β-
tubulin III, was measured by real-time quantitative RT-PCR. This study found that GA had a synergistic effect on the cytotoxity of chemotherapeutic agents against both cell lines. The combination of GA and chemotherapeutic agents could also induce apoptosis in a synergistic manner. The
mRNA levels of TS, ERCC1, BRCA1, tau, and β-
tubulin III were suppressed at 0.009, 0.075, 0.140, 0.267, and 0.624-fold, respectively, when cells were exposed to GA at the concentration of 0.25 μM. These data suggest that GA has a promising role in enhancing the efficacy of
5-FU, Oxa, and Doc in the treatment of
gastric cancer. The potential mechanism would be their synergistic effects on apoptosis induction and the downregulation of chemotherapeutic agent-associated genes.