摘要：

Recent studies have reported menadione (vitamin K3) has inhibitory effect on several types of cancer cells including lung cancer, breast cancer, ovarian cancer, pancreatic cancer and hepatocellular carcinoma, although the effect of menadione on gastric cancer cells is unclear. Therefore, we have investigated the inhibitory effect and the mechanism of menadione on gastric cancer cells. We found that cell viability of AGS (gastric cancer cell) was dramatically inhibited by menadione, while HS738 (non-cancerous gastrointestinal cell) was not influenced by the same dose of menadione treatment. Annexin V-FITC assay results suggested that decreased cell viability was due to the induction of apoptosis and it was confirmed by the results indicating activation of caspase-3 and caspase-9 and cleavage of PARP in the Westernblot. We further investigated the upstream regulatory molecules involved in the apoptosis and discovered that manadione reduces expression of X-linked inhibitor of apoptosis protein (XIAP). XIAP is a potent regulator of apoptosis which binds to and inhibits activity of caspases there by suppressing apoptosis. These results indicate that menadione activates caspase cascade and induces apoptosis mediated by down-regulation of XIAP expression in gastric cancer cells.

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