Morusin is a pure extract from the root bark of Morus australis (Moraceae). In recent years, morusin has been reported to exhibit anti-tumor biological activity in some types of human cancers through different mechanisms. Here, we attempted to investigate the inhibitory effect and mechanism of morusin on gastric cancer. Morusin markedly inhibited gastric cancer cell proliferation by down-regulating CDKs and Cyclins, such as CDK2, CDK4, Cyclin D1 and Cyclin E1. Additionally, morusin suppressed tumor growth in vitro and in vivo. Up-regulation of CDKs and Cyclins in gastric cancer cells was induced by c-Myc binding at the E-Box regions of CDKs and the Cyclin promoter. In addition, compared with the control group, the morusin-treated group showed reduced expression of c-Myc and c-Myc protein binding at the E-Box regions. Based on these results, we overexpressed c-Myc in gastric cancer cells and found that overexpressing c-Myc rescued morusin-induced inhibition of cell proliferation and tumor growth. These results suggest that morusin inhibits cell proliferation and tumor growth by down-regulating c-Myc in human gastric cancer.

Our results imply that GSC has a wide range of LN metastases, including LN within jejunal mesentery in B-II reconstruction cases, and curable resection may obtain better results. Therefore, we suggest that radical operation for B-I patients needs removal of gastroduodenectomy anastomosis and the above LNs, and that B-II patients need removal of 10 cm of jejunum besides gastrojejunostomy anastomosis, and clearance of LN within its mesentery, in addition to B-I GSC.

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