Experimental Research On MS-275Selectively Inhibiting Cell Growth Of Gastric Cancer Cell MKN-45

Objective：Gastric cancer one of most common digestive malignant tumors, is thesecond leading cause of death in various cancer. Surgery has good effect in theearly stomach cancer but the poor effect of middle-late gastric cancer.Chemotherapy and radiation are very limited. Thus, it is necessary to explorenew therapeutic methods to improve the survival of advanced gastric cancer.Inrecent years, studies show that histone acetylation and acetylation playimportant role during the pathogenesis of tumors. Histone deacetylase inhibitorscan induce apoptosis in various tumor cells, including gastric cancer. Butwhether it can selectively kill stomach cancer and simultaneously be unharm tonormal cells remains obscure. To this end, we design the current experiment toexplore the possibility that MS-275can selectively kill stomach cancer cellsMKN-45with emphasis on the potential underlying molecular mechanism.Methods:1) Cell growth curve：Curltured cells MKN-45，GES-1and CHANGLIVERwere exposed to different concentrations of MS-275.Use WST-1method tostudy the growth of cells after MS-275treatment.2) Detection of apoptosis: The change of cell apoptosis was detected by flow cytometry and TUNEL after MS-275treated.3) The DNA content that study the changes of the cell cycle after treated byMS-275was evaluated by flow cytometry.4) We used caspase broad-spectrum inhibitors combined with flow cytometryto analysis the mechanism that caspase plays a potential role inMS-275-mediated apoptosis.5) The influence of MS-275to the protein expression of bax and p21wasassessed by Western blot.Results:1) The growth of gastric cancer cells MKN-45was obviously inhibited bydeacetylase inhibitors MS-275in a time and concentration dependentmanner. But no inhibition on GES-1and CHANGLIVER was observed.2) MS-275can induce apoptosis of gastric cancer cells MKN-45significantly，but have no apoptosis inducible effect on gastric mucosa cells GES-1andCHANGLIVER cells.3) MS-275can stop the growth of MKN-45by arresting it at G0/G1phase.4) Caspase broad spectrum can obviously inhibited the apoptotic functions byMS-275,which illustrate that the apoptosis induced by MS-275is caspasedependent.5) The results of Western Blot demonstrate that MS-275can increase theexpression level of bax and p21.Conclusions：Histone deacetylation inhibitor MS-275can inhibit the growth of gastriccancer cell MKN-45and induce the specific apoptosis in the gastric cancer cells,which may be related to controlling some genes of tumor. The function ofnormal cells seems unaffected by MS-275.