The Mechanism Of Curcumin Inhibits Proliferation Of Gastric Cancer Cells By ATP-Sensitive Potassium Channel

Objective: As the third leading cause of death in men and fourth in women with malignant tumors, gastric cancer is now threatening people’s lives worldwide. Chemotherapy and radiotherapy are employed to treat gastric cancer. However, the side effects of these therapies restrict their application and lower the quality of patients. As a result, research and development of anticarcinogen,which has more potent anti-cancer activity and lower toxicity is imminent. Curcumin, also referred as diferuloylmethane, is one of the main bioactive components of turmeric(Curcuma Longa). As a traditional Chinese medicine, it has many pharmacological functions. In the modern biomedical studies, curcumin was reported effectively impaired proliferation and invasion of many human cancers, and low toxicity. ATP-sensitive potassium channel, also referred to as KATP, is a kind of K+ channels by regulated by intracellular ATP concentration. KATP located on the mitochondrial membrane is called mito KATP(mitochodrial KATP channel). At the early stage of apoptosis, the opening of mitoKATP could inhibit depolarization of mitochondrial membrane to maintain MMP, the opening of mitoKATP channels could protect against apoptosis. In this study, we investigated the effect of curcumin and mito KATP on apoptosis in human gastric cancer cells SGC-7901. Our results will contribute to a deepened understanding of the molecular mechanisms of curcumin’s anti-cancer activity and provide experimental basis for the comprehensive treatment of gastric cancer.Methods: In an vitro study, gastric cancer cell line SGC-7901 was treated with curcumin at serial concentrations and co-administrated with the KATP opener, diazoxide. The effect of curcumin and diazoxide on proliferation were assessed by MTT assay. Mitochondrial membrane potential(MMP) was studied by flow cytometry detection of rhodamine 123 staining. Apoptosis was evaluated by flow cytometry detection of Annexin V/ propidium iodide double staining. In an vivo study, SGC-7901 cells were planted into nude mice as xenografts. Animals were treated with curcumin co-administered with diazoxide. Tumor volume and tumor weight were observed.Results: Curcumin incubation significantly induced loss of MMP in SGC-7901 cells in a dose- dependent manner(P<0.05); the cell apoptotic rate also dramatically increased after curcumin incubation in a dose-dependent manner(P<0.05). After co-administration with diazoxide, which is a mito KATP selective opener, however, we found that both the MMP-loss-inducing and the apoptosis-inducing effects of curcumin in SGC-7901 cells were significantly impaired(all P<0.05). Growth of xenograft tumor was reduced by curcumin but reversed by co-administration of diazoxide in vivo. As a result, the proliferation of SGC-7901 cells was maintained by diazoxide treatment.Conclusion: Curcumin inhibits proliferation of gastric cancer by inducing apoptosis.Impaired mitoKATP opening causes MMP loss, and is involved in curcumin-induced apoptosis in gastric cancer.