Study In Phenyhexyle Isothiocyanate (PHI) Induced Apoptosis Of Gastric Cancer MGC803Cell And The Molecular Mechanism

Objects:To study the effect of phenyhexyle isothiocyanate (PHI) oncell proliferation and apoptosis, histone acetylation and histonemethylation, and Wnt/β-catenin signaling pathway in gastric cancer cell(MGC803). We further study its potential molecular mechanism of apoptosisinducement.Methods:The viability of MGC803cells after treated with PHI waschecked by MTT method. Apoptotic cells were measured by TUNNEL assay. Theexpression of Bcl-2, pro-caspases3which is related to apoptosis weredetected by Western Blot method. And The expression of acetylated histoneH3and H4, methylated histone H3K9and H3K4were also examined.And β-catenin, TCF-4，cyclin D1，c-myc which is related to Wnt/β-cateninsignaling pathway were also examined.Results:(1) PHI inhibited cell growth and induced cells apoptosisand downregulated the expression of Bcl-2、 pro-caspases3,in adose-dependent and time-dependent manner.(2) PHI induced an accumulationof acetylated histone H3, H4, and methylated histone H3K4and decreasedmethylated histone H3K9with the augmenting of time and dose.(3) Afterexposure to PHI for3hours, there was no observable change in theexpression of protein which is related to the Wnt/β-catenin signalingpathway of MGC803cell.After exposure to PHI for7hours, the expressionof the related proteins as β-catenin、cyclinD1、c-myc were decreasedobviously，the expression of TCF-4were also decreased.Conclusions:(1) PHI could inhibit proliferation and induce apoptosis and downregulated the expression of Bcl-2、pro-caspases3in MGC803cells,in a dose-dependent and time-dependent manner.(2)PHI could changethe histone modifications of MGC803cell,improving acetylation of histoneH3, H4, and methylation of histone H3K4, degrading methylation of histoneH3K9.(3) PHI inhibited Wnt/β-catenin signaling pathway in MGC803cell,significantly inhibited β-catenin,and cyclin D1and c-mycdownstream,and also inhibit the expression of TCF-4.(4) PHI might bea potential novel agent in gastric cancer treatment.