阿特拉津(ATZ),一种在全球范围内广泛分布的除草剂,具有在环境暴露后发展各种癌症的潜在风险。然而,ATZ在胆管癌(CCA)中的作用及分子机制,还不清楚。本研究旨在探讨ATZ对体外培养的CCA细胞增殖和迁移的影响。用0.01至100μM的ATZ和17β-雌二醇(E2)处理永生化人胆管细胞(MMNK-1)和三种CCA细胞系(KKU-055,KKU-100和KKU-213B)。结果表明,与E2相似,低剂量(0.01~1μM)的ATZ促进了所有CCA和MMNK-1细胞的增殖.ATZ暴露通过G2/M细胞周期积累增加了KKU-213B和KKU-055细胞的细胞膜和细胞质中的非基因组G蛋白偶联雌激素受体(GPER)表达。这个,反过来,促进CCA细胞的增殖和迁移。ATZ暴露诱导GPER上调和PI3K表达水平增加,p-PI3K,Akt,p-Akt,NF-κB和PCNA。相比之下,ATZ治疗后,GPER拮抗剂G15显著下调GPER/PI3K/Akt/NF-κB通路。这些结果表明ATZ通过GPER/PI3K/Akt/NF-κB途径促进CCA细胞增殖和迁移。这些信息可以提高公众对ATZ污染的认识,以防止CCA的相对风险。
Atrazine (ATZ), an herbicide widely distributed on a global scale, possess a potential risk for the development of various cancers upon environmental exposure. However, the effect and molecular mechanism of ATZ in cholangiocarcinoma (CCA), is still unclear. This study aimed to investigate the effect of ATZ on the proliferation and migration of CCA cell in vitro. Immortalized human cholangiocytes (MMNK-1) and three CCA cell lines (KKU-055, KKU-100 and KKU-213B) were treated with 0.01 to 100 μM of ATZ and 17β-estradiol (E2). The results showed that, similar to E2, low doses (0.01 to 1 μM) of ATZ promoted the proliferation of all CCA and MMNK-1 cells. ATZ exposure increased non-genomic G protein-coupled estrogen receptor (GPER) expression in the cell membrane and cytoplasm of KKU-213B and KKU-055 cells via G2/M cell cycle accumulation. This, in turn, promoted the proliferation and migration of CCA cells. ATZ exposure induced the upregulation of GPER and increased expression levels of PI3K, p-PI3K, Akt, p-Akt, NF-κB and PCNA. In contrast, following ATZ treatment, the GPER antagonist G15 significantly downregulated the GPER/PI3K/Akt/NF-κB pathway. These results suggest that ATZ promotes CCA cell proliferation and migration through the GPER/PI3K/Akt/NF-κB pathway. This information can enhance public health awareness regarding ATZ contamination to prevent the relative risk of CCA.