Experimental Research On The Histone Deacetylase Inhibitor MS-275 Selevtively Inhibiting Cell Growth Of Gastric Cancer Cell SGC-7901

AIM:The histone deacetylase inhibitor(HDACi) can selectively induce apoptosis and differentiation on many kinds of tumor cells, but it has no evident cytotoxic effect on normal cells. Because of the specificity, it has become the target as a new anticancer agents and some of them has entered the clinical research phase. This paper aims to investigate the antiproliferation effect and its mechanism of the HDACi MS-275 on inhibiting the gastric cancer cell SGC-7901 and normal cells GES-1 and CHANGLIVER to provide experimental basis for clinical practice.METHODS:1. Cultured cells SGC-7901, GES-1 and CHANGLIVER were exposed to different concentrations of MS-275 for different durations. The growth inhibition was evaluated by WST-1 assay(cell proliferation assay), to prove that if MS-275 can only induce cell growth arrest on gastric cancer cell but not on normal cell;2. Cell apoptosis was detected by AnnexinV/PI-labeled flow cytometry;3. DNA fragmentation in nucleus in SGC-7901 cells can be observed by TUNEL assay, which can testify MS-275 mediated apoptosis from another aspect;4. Cell cycle status after treated by MS-275 was reflected by the DNA content which was detected by flow cytometry;5. Use the caspase inhibitor to make out what the role that caspase plays in MS-275-mediated apoptosis and investigate which apoptosis pathway MS-275 involved in;6. The change of Bcl-2 expression after exposed to MS-275 was detected by Western Blot. RESULTS:1. MS-275 can inhibit cell growth and induce cell apoptosis in SGC-7901 cell lines in a concentration and time dependent manner, but has no evident effect on normal cells lines;2. MS-275 can selectively iuduce cell death in SGC-7901 cell but not for GES-1 and CHANGLIVER cells;3. TUNEL assay proved that MS-275 can induce DNA fragmentation in the nucleus of SGC-7901 cells, which was an important symbol of cell apoptosis;4. MS-275 can arrest the cell cycle of SGC-7901 at Gl checkpoint, and along with the drug dealing, Gl cells increased obviously;5. Caspase inhibitor can suppress the apoptosis caused by MS-275, which demonstrated that MS-275 induces caspase-dependent apoptosis;6. After the exposure to MS-275, Bc1-2 started to downregulates and it turned out to be a concentration and time dependent manner.CONCLUSION:MS-275 can selectively induce apoptosis in gastric cancer cells in vitro, but not in normal cells; MS-275 can function through inducing apoptosis by caspase-dependent pathway and arresting cell cycle; In addition, MS-275 can also downregulate Bcl-2 which can surpress apoptosis. It would be the new molecular targeted drug for clinical treatment on gastric cancer.