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Effect of Valproic Acid on proliferation and apoptosis of esophageal cancer cells and study on its antitumor activity mechanism |
YANG Jing-rong1 LIU Ya-ming1 ZHANG Jin-can2 ZENG Zhi-yong1▲ |
1.Department of Cardiothoracic Surgery, the 900th Hospital of the Joint Support Force (the Former Fuzhou General Hospital of Nanjing Military Region), Fujian Province, Fuzhou 350025, China;
2.Fuzong Clinical College of Fujian Medical University, Fujian Province, Fuzhou 350025, China |
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Abstract Objective To explore the effect of Valproic Acid (VPA) on proliferation and apoptosis of esophageal cancer cells,and expression of Bcl-2,Caspase protein,as well as molecular mechanisms of signal transduction pathways. Methods ECa-109 cell line of esophageal cancer was cultured with PRMI1640 medium, and grouped according to solvent control and solubility gradient:blank control and VPA 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L, 2.0 mmol/L, 4.0 mmol/L.After treating cells for 24, 48 and 72 hours according to different drug concentrations, the changes of esophageal cancer ECa-109 cells were observed, and different detection methods were used to detect the changes of cell viability, apoptosis and cycle of esophageal cancer ECa-109 cells.Western Blot was used to detect CyclinD1, p21, Survivin, Bcl-2,Caspase protein and PI3K/Akt and MAPK signal transduction pathway changes. Results VPA showed different extent changes on vitality, proliferation, differentiation of ECa-109 cells, could induce cell apoptosis by inducing cell cycle arrest.Western Blot experiment results showed that VPA could affect the expression of Bcl-2, Survivin and Caspase proteins in ECa-109 cells.VPA could significantly reduce the expression level of CyclinD1 protein in ECa-109 cells and increase the expression of p21 protein, which influenced the phosphorylation of key proteins such as AKT and MAPK in the signaling pathway PI3K/Akt and MAPK pathway. Conclusion VPA has an effect on the proliferation and apoptosis of esophageal cancer cells and it is concentration-dependent, which can affect the growth of esophageal cancer cells through the signaling pathways of multiple protein kinase pathways, the expression of survival proteins, the expression of PI3K/Akt and MAPK signaling pathways.
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|
[3] |
吴健,王晶晶,杨鲸蓉,等.组蛋白去乙酰化酶抑制剂对食管癌细胞抗肿瘤活性及其相关机制的研究进展[J].东南国防医药,2018,20(4):394-398.
|
[1] |
郭琼.甲基化、乙酰化修饰改变对食管癌细胞生长及相关基因表达的研究[D].乌鲁木齐:新疆医科大学,2015.
|
[2] |
王小兵.MIC1 在食管鳞癌诊断和抗体靶向治疗中的意义及其作为肿瘤干细胞治疗靶点的初步研究[D].北京:北京协和医学院,2014.
|
[4] |
Wahaib K,Beggs AE,Campbell H,et al.Panobinostat:A histone deacetylase inhibitor for the treatment of relapsed or refractory multiple myeloma[J].Am J Health Syst Pharm,2016,73(7):441-450.
|
[5] |
Conte M,Palma RD,Altucci L.HDAC inhibitors as epigenetic regulators for cancer immunotherapy[J].Int J Biochem Cell Biol,2018,98:65-74.
|
[6] |
Carolina V D A,Julia H,César C,et al.Epigenetic priming in cancer initiation[J].Trends Cancer,2018,4(6):408-417.
|
[7] |
Knipstein J,Gore L.Entinostat for treatment of solid tumors and hematologic malignancies[J].Expert Opin Investig Drugs,2011,20(10):1455-1467.
|
[8] |
Ozaki T,Wu D,Sugimoto H,D,et al.Runt-related transcription factor 2 (RUNX2) inhibits p53-dependent apoptosis through the collaboration with HDAC6 in response to DNA damage[J].Cell Death Dis,2019,4(4):e610.
|
[9] |
Lopez G,Bill KL,Bid HK,et al.HDAC8,a potential therapeutic target for the treatment of malignant peripheral nerve sheath tumors (MPNST)[J].PLoS One,2015,10(7):e133302.
|
[10] |
Saito T,Nishida K,Furumatsu T,et al.Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes[J].Osteoarthritis Cartilage,2013,21(1):165-174.
|
[11] |
Yoon S,Eom GH.HDAC and HDAC inhibitor:from cancer to cardiovascular diseases[J].Chonnam Med J,2016,52(1):1-11.
|
[12] |
Yang H,Maddipoti S,Quesada A,et al.Analysis of class Ⅰand Ⅱ histone deacetylase gene expression in human leukemia[J].Leuk Lymphoma,2015,56(12):3426-3433.
|
[13] |
Glaser KB.HDAC inhibitors:Clinical update and mechanism-based potential[J].Biochem Pharmacol,2007,74(5):659-671.
|
[14] |
Xu J,Zhou JY,Wei WZ,et al.Sp1-mediated TRAIL induction in chemosensitization[J].Cancer Res,2008,68(16):6718-6726.
|
[15] |
Fulda S.Modulation of TRAIL-induced apoptosis by HDAC inhibitors[J].Curr Cancer Drug Targets,2008,8(2):132-140.
|
[16] |
Zhou H,Cai Y,Liu D,et al.Pharmacological or transcriptional inhibition of both HDAC1 and 2 leads to cell cycle blockage and apoptosis via p21Waf1/Cip1 and p19INK4d upregulation in hepatocellular carcinoma[J].Cell Prolif,2018,51(3):e12447.
|
[17] |
Arts J,King P,Marien A,et al.JNJ-26481585,a novel"second-generation" oral histone deacetylase inhibitor,shows broad-spectrum preclinical antitumoral activity[J].Clin Cancer Res,2009,15(22):6841-6851.
|
[18] |
Witt O,Sand K,Pekrun A.Butyrate induced erythroid differentiation of human K562 cells involves inhibition of ERK and activation of p38 MAP kinase pathways[J].Blood,2000,95(7):2391-2396.
|
[19] |
Peng Z,Guo Z,Ying W,et al.Histone deacetylase inhibitors inhibit the proliferation of gallbladder carcinoma cells by suppressing AKT/mTOR signaling[J].PLoS One,2015,10(8):e136193.
|
|
|
|