[The relationship of mTOR signaling pathway and histone acetylation in human gastric cancer cell lines].
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).


CONCLUSIONS
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.
Renji Hospital, Shanghai Institute of Digestive Disease, School of Medicine, Shanghai Jiaotong University, Shanghai, 200001 P. R. China.
Dan-feng
DF
Sun
Jing-yuan
JY
Fang
Yan-jie
YJ
Zhang
Xiao-qing
XQ
Tian
Hong-yin
HY
Zhu
En-ling
EL
Li
Wei-qi
WQ
Gu
Guan-feng
GF
Shen
D000107:Acetylation / Q000187:drug effects; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D005434:Flow Cytometry; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D002867:Chromones; D050759:Cyclin-Dependent Kinase Inhibitor p21; C087000:EIF4EBP1 protein, human; D006657:Histones; D006877:Hydroxamic Acids; D009025:Morpholines; D010750:Phosphoproteins; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C012589:trichostatin A; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus