Yang Xuefeng, Huang Handong, Wang Maijian, Zheng Xingbin, Xu Jie, Xie Ming
Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.
School of Public Health, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.
Mol Med Rep. 2017 Aug;16(2):2211-2216. doi: 10.3892/mmr.2017.6817. Epub 2017 Jun 20.
Nonylphenol (NP) is a well-known endocrine-disrupting chemical (EDC), which can enhance the progression of cancer by functioning as an estrogen‑like factor. In the present study, the effects of different concentrations of NP on COLO205 colorectal cancer (CRC) cells were examined. The results of flow cytometric analysis revealed that NP significantly decreased the proportion of cells in the G0/G1 phase in a dose‑dependent manner, which was accompanied by a marginal increase in the proportions of cells in S and G2/M phases. NP did not induce apoptosis, whereas estradiol (E2) did induce apoptosis. To elucidate the mechanisms underlying the action of NP on COLO205 cells, the transcriptional levels of extracellular signal‑regulated kinase (ERK)1, ERK2 and phosphoinositide 3‑kinase (PI3K) were assessed using reverse transcription‑quantitative polymerase chain reaction analysis. The expressions levels of ERK1, ERK2 and PI3K were increased by treatment with NP in a dose‑dependent manner. On examining protein levels, the expression of PI3K p38 was increased by NP and E2, and the expression of ERK1/2 was increased by NP. The phosphorylation of the ERK protein was significantly increased by treatment with NP at a high concentration (10‑4 M; P<0.01), but significantly decreased by E2 (P<0.01). Two key proteins in the transforming growth factor (TGF)β pathway (c‑Fos and SnoN) were selected for analysis using western blot analysis in the COLO205 cells treated with NP and E2. The expression levels of c‑Fos and SnoN were significantly increased by treatment with E2 (10‑7 M; P<0.01) and NP (10‑7‑10‑4 M; P<0.01). Taken together, these results indicated that NP affected the development of CRC via the ERK signaling pathway and TGFβ pathway.
壬基酚（NP）是一种著名的内分泌干扰化学物质（EDC），它可以作为一种雌激素样因子促进癌症进展。在本研究中，检测了不同浓度的NP对COLO205结肠直肠癌（CRC）细胞的影响。流式细胞术分析结果显示，NP以剂量依赖性方式显著降低了G0/G1期细胞的比例，同时S期和G2/M期细胞的比例略有增加。NP未诱导细胞凋亡，而雌二醇（E2）可诱导细胞凋亡。为了阐明NP对COLO205细胞作用的潜在机制，使用逆转录-定量聚合酶链反应分析评估细胞外信号调节激酶（ERK）1、ERK2和磷酸肌醇3-激酶（PI3K）的转录水平。NP处理以剂量依赖性方式增加了ERK1、ERK2和PI3K的表达水平。在检测蛋白水平时，NP和E2增加了PI3K p38的表达，NP增加了ERK1/2的表达。高浓度（10-4 M）的NP处理显著增加了ERK蛋白的磷酸化水平（P<0.01），而E2则显著降低了ERK蛋白的磷酸化水平（P<0.01）。在NP和E2处理的COLO205细胞中，选择转化生长因子（TGF）β途径中的两个关键蛋白（c-Fos和SnoN）进行蛋白质印迹分析。E2（10-7 M；P<0.01）和NP（10-7-10-4 M；P<0.01）处理显著增加了c-Fos和SnoN的表达水平。综上所述，这些结果表明NP通过ERK信号通路和TGFβ途径影响CRC的发展。
