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CYP2E1 changes the biological function of gastric cancer cells via the PI3K/Akt/mTOR signaling pathway

Rui-Ying Wang1, Xiao-Wei Chen1, Wen-Wen Zhang1

  • 1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, P.R. China.

Molecular Medicine Reports
|January 25, 2020
PubMed

Insights

Cytochrome P450 2E1 (CYP2E1) overexpression promotes gastric cancer cell proliferation and invasion by activating the PI3K/Akt/mTOR pathway, inhibiting apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Gastric cancer (GC) remains a significant global health challenge.
  • Understanding the molecular mechanisms driving GC progression is crucial for developing effective therapies.
  • Cytochrome P450 family 2 subfamily E polypeptide 1 (CYP2E1) has been implicated in various cancers, but its specific role in GC requires further elucidation.

Purpose of the Study:

  • To investigate the role of CYP2E1 in gastric cancer cell proliferation, invasion, and apoptosis.
  • To explore the relationship between CYP2E1 expression and the PI3K/Akt/mTOR signaling pathway in GC.

Main Methods:

  • Western blotting to assess CYP2E1 expression in GC cells (MGC-803) and normal cells (GES-1).
  • Lentiviral vector-mediated overexpression of CYP2E1 in MGC-803 cells.
  • Cell proliferation (Cell Counting Kit-8), apoptosis (flow cytometry), migration, and invasion assays.
  • RT-qPCR and western blotting to analyze the PI3K/Akt/mTOR pathway components.
  • Treatment with PI3K inhibitor LY294002 to validate pathway involvement.

Main Results:

  • CYP2E1 expression was significantly different between GC and normal cells, with overexpression noted in GC cells.
  • Overexpression of CYP2E1 promoted GC cell proliferation and invasion while inhibiting apoptosis.
  • CYP2E1 overexpression upregulated mTOR mRNA and increased the phosphorylation of Akt, mTOR, and P70S6K.
  • Inhibition of PI3K by LY294002 downregulated the expression of PI3K, CYP2E1, Akt, mTOR, and P70S6K.

Conclusions:

  • CYP2E1 plays a critical role in promoting gastric cancer progression.
  • The oncogenic effects of CYP2E1 in GC are mediated through the activation of the PI3K/Akt/mTOR signaling pathway.
  • Targeting CYP2E1 or this pathway may offer a therapeutic strategy for gastric cancer.
Keywords:
gastric cancercYP2e1cytological functionPi3K/akt/mTorlY294002

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