Potent effects of dioscin against gastric cancer in vitro and in vivo.

BACKGROUND: We previously reported the effect of dioscin on human gastric carcinoma SGC-7901 cells, but its effects on other gastric cancers are still unknown.

PURPOSE: The present paper aimed to demonstrate the activity of dioscin against human gastric carcinoma MGC-803 and MKN-45.

STUDY DESIGN: In our study, MGC-803 and MKN-45 cells were used to examine the effects of dioscin on human gastric carcinoma in vitro. The effects of dioscin against human gastric carcinoma in vivo were accomplished by the xenografts of MGC-803 cells in BALB/c nude mice.

METHODS: AO/EB and DAPI staining, TEM, single cell gel electrophoresis and flow cytometry assays were used in cell experiments. Then, an iTRAQ-based proteomics approach, DNA and siRNA transfection experiments were carried out for mechanism investigation.

RESULTS: In MGC-803 cells, dioscin caused DNA damage and mitochondrial change, induced ROS generation, Ca(2+) release and cell apoptosis, and blocked cell cycle at S phase. In vivo results showed that dioscin significantly suppressed the tumor growth of MGC-803 cell xenografts in nude mice. In addition, dioscin markedly inhibited cell migration, caused Cytochrome c release and adjusted mitochondrial signal pathway. Then, an iTRAQ-based proteomics approach was carried out and 121 differentially expressed proteins were found, in which five biomarkers associated with cell cycle, apoptosis and migration were evaluated. Dioscin significantly up-regulated the levels of GALR-2 and RBM-3, and down-regulated CAP-1, Tribbles-2 and CliC-3. Furthermore, overexpressed DNA transfection of CAP-1 enhanced cell migration and invasion, which was decreased by dioscin. SiRNA to Tribbles-2 affected the protein levels of Bcl-2, Bax and MAPKs, suggesting that dioscin decreased Tribbles-2 level leading to cell apoptosis.

CONCLUSION: Our works confirmed the activity of dioscin against gastric cancer. In addition, this work also provided that dioscin is a new potent candidate for treating gastric cancer in the future.