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

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Aug;24(4):387-91.
[Article in Chinese]

Abstract

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.

MeSH terms

  • Acetylation / drug effects
  • Adaptor Proteins, Signal Transducing / metabolism
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chromones / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Flow Cytometry
  • Histones / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Morpholines / pharmacology
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Polymerase Chain Reaction
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sirolimus / pharmacology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / physiopathology
  • TOR Serine-Threonine Kinases

Substances

  • Adaptor Proteins, Signal Transducing
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Chromones
  • Cyclin-Dependent Kinase Inhibitor p21
  • EIF4EBP1 protein, human
  • Histones
  • Hydroxamic Acids
  • Morpholines
  • Phosphoproteins
  • RNA, Messenger
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • trichostatin A
  • Protein Kinases
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • Sirolimus