Abstract: Objective: To identify the mechanism related to miRNA pathway which plays a role in the anti-tumor effects of Diallyl disulfide. Methods: Gastric cancer cell line MGC-803 were divided into DADS treatment group, miR-222 mimics group, miR-222 inhibitors group, negative control group; MGC-803 cells were treated With 0, 25, 50, 100, 200, 400μmol/L DADS respectively; miR-222 mimics, miR-222 inhibitors and scramble sequence were transfected in MGC-803 cells respectively. A qRT-PCR was employed for detecting the expression of miR-222 in MGC-803 cells. Western blotting was conducted to detect the expressions of TIMP3 protein in MGC-803 cells. The proliferation and invasion ability of MGC-803 cells in vitro were evaluated by MTT and Transwell invasion assays. Results: miR-222 expression was down- regulated with increasing doses of DADS( P<0. 05); DADS could significantly inhibit MGC-803 cell proliferation and invasion capacity, ectopic expression of miR-222 could significantly promote MGC-803 cell proliferation and invasion capacity. Furthermore, gastric cancer cells treated with combination of DADS and miR-222 inhibitors showed significant inhibition of cell proliferation and invasion than treated with DADS alone( P<0. 05); The level of TIMP3 protein was inhibited by treated with DADS in MGC-803 cells, overexpression of miR-222 resulted in increased TIMP3 protein levels. Furthermore, The level of TIMP3 protein was inhibited treated with combination of DADS and miR-222 inhibitors than treated with DADS when alone in MGC-803 cells( P<0. 05). Conclusion: DADS suppresses proliferation and invasion in human gastric cancer cells through targeting TIMP3 by down-regulation of miR-222.

Key words: Gastric cancer, MiR-222, Diallyl Disulfide, Proliferation and Invasion