Affiliation:
1. School of Life Sciences, Southwest University, Chongqing, 400715, China
2. State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, China
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.
Funder
Chongqing Postdoctoral Science Special Foundation
China Postdoctoral Science Foundation
Innovation Program for Chongqing's Overseas Returnees
SWU Undergraduate Innovation and Entrepreneurship Training Programs
Fundamental Research Funds for the Central Universities
Chongqing Research Program of Basic Research and Frontier Technology
National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Reference51 articles.
1. Lee H.J.; Song I.C.; Yun H.J.; Jo D.Y.; Kim S.; CXC chemokines and chemokine receptors in gastric cancer: From basic findings towards therapeutic targeting. World J Gastroenterol 2014,20(7),1681-1693
2. Li B.; Liu H.Y.; Guo S.H.; Sun P.; Gong F.M.; Jia B.Q.; Detection of microsatellite instability in gastric cancer and dysplasia tissues. Int J Clin Exp Med 2015,8(11),21442-21447
3. Lee H.S.; Kim W.H.; Kwak Y.; Koh J.; Bae J.M.; Kim K.M.; Chang M.S.; Han H.S.; Kim J.M.; Kim H.W.; Chang H.K.; Choi Y.H.; Park J.Y.; Gu M.J.; Lhee M.J.; Kim J.Y.; Kim H.S.; Cho M.Y.; Gastrointestinal Pathology Study Group of Korean Society of Pathologists; Molecular Pathology Study Group of Korean Society of Pathologists. Molecular testing for gastrointestinal cancer. J Pathol Transl Med 2017,51(2),103-121
4. Frei E.; Clinical cancer research: An embattled species. Cancer 1982,50(10),1979-1992
5. Wu H.; Wang W.; Tong S.; Wu C.; Nucleostemin regulates proliferation and migration of gastric cancer and correlates with its malignancy. Int J Clin Exp Med 2015,8(10),17634-17643
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