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Chinese Journal of Medical Genetics ; (6): 387-391, 2007.
Article in Chinese | WPRIM | ID: wpr-247310

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the relationship between mammalian target of rapamycin (mTOR) signaling pathway and histone acetylation in cell survival, cell cycle, gene expression and protein level on human gastric cancer cells.</p><p><b>METHODS</b>Human gastric cancer cell lines, MKN45 and SGC7901 were treated with trichostatin A, rapamycin and/or LY294002, a PI3K inhibitor. Cell viability was analyzed by methylthiazolyl tetrazolium. Cell cycle distribution was evaluated by flow cytometry. The transcription level of p21(WAF1) gene was detected by using real-time polymerase chain reaction. Proteins were detected by Western blotting.</p><p><b>RESULTS</b>Cell viability remarkably reduced after treatment by more than two drugs (P< 0.01). Through flow cytometry assessment, MKN45 cells were arrested in G2 phase (P< 0.05), while SGC7901 cells were in G2 or G1 phase (P< 0.05) whether treated with single or more than two drugs. The expression of p21(WAF1) mRNA was remarkably increased in the gastric cancer cells treated with conjoined drugs (P< 0.01). Phosphorylation of Akt, p70S6K and 4E-BP1 was significantly reduced in cells treated with conjoined drugs (P< 0.01). And histone acetylation of H4/H3 was also increased in cells treated with conjoined drugs (P< 0.01).</p><p><b>CONCLUSION</b>mTOR singnaling pathway has an important relationship with histone acetylation in gastric cancer cell lines. There is a co-effect of mTOR inhibitor and histone deacetylase inhibitor on gastric cancer cells.</p>


Subject(s)
Humans , Acetylation , Adaptor Proteins, Signal Transducing , Metabolism , Blotting, Western , Cell Cycle , Cell Line, Tumor , Cell Survival , Chromones , Pharmacology , Cyclin-Dependent Kinase Inhibitor p21 , Genetics , Flow Cytometry , Histones , Metabolism , Hydroxamic Acids , Pharmacology , Morpholines , Pharmacology , Phosphoproteins , Metabolism , Phosphorylation , Polymerase Chain Reaction , Protein Kinases , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , RNA, Messenger , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Ribosomal Protein S6 Kinases, 70-kDa , Metabolism , Signal Transduction , Physiology , Sirolimus , Pharmacology , Stomach Neoplasms , Metabolism , Pathology , TOR Serine-Threonine Kinases
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