The reduction of IL-6 gene expression, pAKT, pERK1/2, pSTAT3 signaling pathways and invasion activity by gallic acid in prostate cancer PC3 cells
The reduction of IL-6 gene expression, pAKT, pERK1/2, pSTAT3 signaling pathways and invasion activity by gallic acid in prostate cancer PC3 cells
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DOI：
10.1016/j.biopha.2016.09.046
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发表时间：
2016-12-01
影响因子：
7.5
通讯作者：
Valipour, Parisa
中科院分区：
文献类型：
--
作者：
Heidarian, Esfandiar;Keloushadi, Mahnaz;Valipour, Parisa
前列腺癌（PC）是男性中最常见的癌症之一。前列腺癌的进展与白细胞介素-6（IL-6）的细胞水平的增加相关。没食子酸（GA）是一种多羟基酚类化合物，具有抑制癌细胞生长的作用。本研究的目的是评估GA处理对人前列腺癌PC 3细胞的细胞活力、增殖、侵袭、IL-6基因表达、IL-6分泌、pSTAT 3、pERK 1/2和pAKT信号蛋白的细胞水平的影响。通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑（MTT）测定评价用GA（0-120 mM）处理后的PC 3细胞活力。采用实时荧光定量聚合酶链反应检测IL-6的表达。Western blotting法检测细胞内pSTAT 3、pERK 1/2和pAKT信号蛋白的浓度。侵袭实验检测PC 3细胞的侵袭能力。GA处理48 h后细胞活力、增殖、侵袭能力、pSTAT 3、pERK 1/2和pAKT信号蛋白水平均呈剂量依赖性下降。GA处理后PC 3细胞IL-6水平及其基因表达明显降低。结果表明，GA下调PC 3细胞IL-6表达，降低IL-6蛋白水平，导致pSTAT 3、pERK 1/2和pAKT信号蛋白表达减少，从而降低PC 3细胞的存活、增殖和侵袭能力。因此，似乎GA可以被认为是治疗前列腺癌的抗癌剂。(C)2016 Elsevier Masson SAS。All rights reserved.
Prostate cancer (PC) is one of the most common cancers among men. Progression of prostate cancer is associated with an increase in cellular level of interleukin-6 (IL-6). Gallic acid (GA) is a polyhydroxy phenolic compound which can inhibit the growth of cancer cells. The aim of this study was to evaluate the effects of GA treatment on cell viability, proliferation, invasion, IL-6 gene expression, IL-6 secretion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins in human prostate cancer PC3 cells. PC3 cells viability after treatment with GA (0-120 mM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay. The expression of IL-6 was investigated using real-time polymerase chain reaction. Cellular concentration of pSTAT3, pERK1/2, and pAKT signaling proteins were determined by Western blotting technic. PC3 cells invasion was assessed by invasion assay test. Treatment with GA caused a significant decrease in cell viability, proliferation, invasion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins after 48 h in a dose-dependent manner. The level of IL-6 and its gene expression decreased significantly in PC3 cells treated with GA. Our results show that IL-6 down-regulation and decreased IL-6 protein level in PC3 cells by GA resulted in diminishing of pSTAT3, pERK1/2, and pAKT signaling proteins which lead to the reduction of the cell survival, proliferation, and invasion in PC3 cells. Therefore, it seems that GA can be considered an anticancer agent in the treatment of prostate cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.