Cantharidin Induces G2/M Phase Arrest And Apoptosis In Human Gastric Cancer SGC-7901and BGC-823 Cells

Background:Gastric cancer, is the fourth most prevalent malignant disease and the second leading cause of cancer-related deaths worldwide. It is characterized by high mortality and short median survival time, since it is too late when the diagnosis is arrived at, in part, due to its asymptomatic nature in early stages. Nowadays, it remains a formidable disease to resolve although great progresses have been made in its treatment. Currently, the main therapeutic modality involves surgery, radiation and chemotherapy. Induction of cell cycle arrest and cell apoptosis, which has been proved to be able to induce the cancer cell death, may be a considered strategy to deal with gastric cancer. Cantharidin, is an effective component extracted from blister beetle, and it is one of many natural products used in traditional Chinese medicine. It has been demonstrated to show potent anticancer activities on many types of human cancer cells. However, the activity of cantharidin on gastric cancer remains unclear.Aims:We aimed to study the effect of cantharidin in human gastric cancer cells and to explore the underlying mechanisms.Methods:(1) The human gastric cancer cell lines SGC-7901 and BGC-823 cells were treated with cantharidin.(2) MTS assay was employed to examine celluar proliferation.(3) Flow cytometry was used to analyze cell cycle.(4) Flow cytometry was used to analyze celluar apoptosis.(5) Western blot analysis was used to determine protein expression. Results:We found that cantharidin inhibited the proliferation of human gastric cancer cells SGC-7901 and BGC-823 in a dose-dependent and time-dependent manner in vitro. And it induced the G2/M phrase arrest and celluar apoptosis in a dose-dependent manner. Moreover, cantharidin increased the level of P21, Caspase-7,-8,-9, activated Caspase-3, PARP and Bad, but decreased the levels of CDK1, Cyclin A, Cyclin B, Bcl-2 and Bid. Conclusions:Our results suggested that cantharidin may inhibit the proliferation of human gastric cancer cells SGC-7901 and BGC-823 in vitro by inducing the G2/M phase arrest and cell apoptosis.It may induce celluar G2/M phase arrest by regulating cycle-associated proteins and induce celluar apoptosis via activating caspase cascade and/or regulating Bcl-2 family proteins.