PMID- 17680526 OWN - NLM STAT- MEDLINE DCOM- 20090327 LR - 20211203 IS - 1003-9406 (Print) IS - 1003-9406 (Linking) VI - 24 IP - 4 DP - 2007 Aug TI - [The relationship of mTOR signaling pathway and histone acetylation in human gastric cancer cell lines]. PG - 387-91 AB - OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. FAU - Sun, Dan-feng AU - Sun DF AD - Renji Hospital, Shanghai Institute of Digestive Disease, School of Medicine, Shanghai Jiaotong University, Shanghai, 200001 P. R. China. FAU - Fang, Jing-yuan AU - Fang JY FAU - Zhang, Yan-jie AU - Zhang YJ FAU - Tian, Xiao-qing AU - Tian XQ FAU - Zhu, Hong-yin AU - Zhu HY FAU - Li, En-ling AU - Li EL FAU - Gu, Wei-qi AU - Gu WQ FAU - Shen, Guan-feng AU - Shen GF LA - chi PT - Journal Article PL - China TA - Zhonghua Yi Xue Yi Chuan Xue Za Zhi JT - Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics JID - 9425197 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (CDKN1A protein, human) RN - 0 (Cell Cycle Proteins) RN - 0 (Chromones) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (EIF4EBP1 protein, human) RN - 0 (Histones) RN - 0 (Hydroxamic Acids) RN - 0 (Morpholines) RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 3X2S926L3Z (trichostatin A) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Acetylation/drug effects MH - Adaptor Proteins, Signal Transducing/metabolism MH - Blotting, Western MH - Cell Cycle/drug effects MH - Cell Cycle Proteins MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Chromones/pharmacology MH - Cyclin-Dependent Kinase Inhibitor p21/genetics MH - Flow Cytometry MH - Histones/*metabolism MH - Humans MH - Hydroxamic Acids/pharmacology MH - Morpholines/pharmacology MH - Phosphoproteins/metabolism MH - Phosphorylation/drug effects MH - Polymerase Chain Reaction MH - Protein Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Signal Transduction/drug effects/*physiology MH - Sirolimus/pharmacology MH - Stomach Neoplasms/metabolism/pathology/physiopathology MH - TOR Serine-Threonine Kinases EDAT- 2007/08/08 09:00 MHDA- 2009/03/28 09:00 CRDT- 2007/08/08 09:00 PHST- 2007/08/08 09:00 [pubmed] PHST- 2009/03/28 09:00 [medline] PHST- 2007/08/08 09:00 [entrez] AID - 940624087 [pii] PST - ppublish SO - Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Aug;24(4):387-91.