Histone Deacetylase Inhibitor Trichostatin A Suppresses Cell Proliferation and Induces Apoptosis by Regulating the PI3K/AKT Signalling Pathway in Gastric Cancer Cells

Author(s): Xinli An, Zekun Wei, Botian Ran, Hao Tian, Hongyu Gu, Yan Liu, Hongjuan Cui*, Shunqin Zhu*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 17 , 2020

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Abstract:

Background: Gastric cancer, a common malignant tumour worldwide, has a relatively poor prognosis and is a serious threat to human health. Histone Deacetylase Inhibitors (HDACi) are anticancer agents that are known to affect the cell growth of different cancer types. Trichostatin A (TSA) selectively inhibits the class I and II mammalian Histone Deacetylase (HDAC) family enzymes and regulates many cell processes. Still, the underlying mechanisms of HDACs are not fully understood in gastric cancer.

Objective: This study aims to investigate the antitumor effect and the mechanism of growth modulation of gastric cancer cells by TSA.

Methods: The cell proliferation of gastric cancer cells was measured by MTT and BrdU immunofluorescence assays. Soft agar assay was used to detect the colony formation ability of gastric cancer cells. Flow cytometry was used to examine cell cycle and apoptosis. Western blot was employed to detect protein expression of target factors.

Results: TSA inhibits the proliferation of MKN-45 and SGC-7901 cells and leads to significant repression of colony number and size. Flow cytometry assays show TSA induces cell cycle arrest at G1 phase and apoptosis, and TSA effects the expression of related factors in the mitochondrial apoptotic signalling and cell cycle-related regulatory pathways. Furthermore, TSA increased histone H3K27 acetylation and downregulated the expression of PI3K and p-AKT.

Conclusion: Downregulating PI3K/AKT pathway activation is involved in TSA-mediated proliferation inhibition of gastric cancer.

Keywords: Trichostatin A (TSA), proliferation, apoptosis, PI3K/AKT, gastric cancer, inhibitor.

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Article Details

VOLUME: 20
ISSUE: 17
Year: 2020
Published on: 12 November, 2020
Page: [2114 - 2124]
Pages: 11
DOI: 10.2174/1871520620666200627204857
Price: $65

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