Yang Xuefeng, Huang Handong, Wang Maijian, Zheng Xingbin, Xie Ming, Xu Jie
Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
School of Public Health, Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Oncol Lett. 2019 Feb;17(2):2498-2506. doi: 10.3892/ol.2018.9846. Epub 2018 Dec 18.
Previous studies have indicated the potential role of estrogen in the development and prognosis of colorectal cancer (CRC). Nonylpheno (NP) is an endocrine-disrupting chemical, which may influence the development of estrogen-dependent types of cancer. However, the molecular mechanism of NP in the development of CRCs remains unclear. In the present study, various concentrations of NP were used to treat COLO205 CRC cells, and the expression of protein kinase C ζ (PKCζ) was knocked down using PKCζ small interfering RNA. The effects of NP in various concentrations on the cell cycle and apoptosis of COLO205 cells were examined, and the change in the expression level of PKCζ was analyzed. The results indicated that NP may significantly induce proliferation of COLO205 CRC cells, and significantly reduce cell apoptosis. However, suppression of PKCζ expression may inhibit proliferation, while NP could reduce this inhibition. The results of a western blot analysis indicated that the expression level of cyclin D1 and E were significantly increased following NP treatment, and the expression of p27 was significantly decreased. The phosphorylation of PKCζ and extracellular-signal-regulated kinase (ERK)1/2 was significantly increased following NP treatment in a dose-dependent manner. Overall, NP induced human CRC COLO205 cell proliferation and inhibited the apoptotic rate of COLO205 cells by increasing the activity of PKCζ and ERK1/2.
先前的研究表明雌激素在结直肠癌（CRC）的发生发展及预后中具有潜在作用。壬基酚（NP）是一种内分泌干扰化学物质，可能影响雌激素依赖性癌症的发展。然而，NP在结直肠癌发生发展中的分子机制仍不清楚。在本研究中，使用不同浓度的NP处理COLO205结直肠癌细胞，并使用PKCζ小干扰RNA敲低蛋白激酶Cζ（PKCζ）的表达。检测了不同浓度的NP对COLO205细胞周期和凋亡的影响，并分析了PKCζ表达水平的变化。结果表明，NP可显著诱导COLO205结直肠癌细胞增殖，并显著降低细胞凋亡。然而，抑制PKCζ表达可抑制增殖，而NP可减轻这种抑制作用。蛋白质印迹分析结果表明，NP处理后细胞周期蛋白D1和E的表达水平显著升高，p27的表达显著降低。NP处理后，PKCζ和细胞外信号调节激酶（ERK）1/2的磷酸化呈剂量依赖性显著增加。总体而言，NP通过增加PKCζ和ERK1/2的活性诱导人结直肠癌COLO205细胞增殖并抑制其凋亡率。
