阿特拉津（ATZ）是一种在全球范围内广泛使用的除草剂，暴露于环境中具有引发多种癌症的潜在风险。然而，ATZ在胆管癌（CCA）中的作用和分子机制仍不清楚。本研究旨在探讨ATZ对体外CCA细胞增殖和迁移的影响。用 0.01 至 100 μM 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 类似，低剂量（0.01 至 1 μM）ATZ 促进所有 CCA 和 MMNK-1 细胞的增殖。 ATZ 暴露通过 G2/M 细胞周期积累增加 KKU-213B 和 KKU-055 细胞细胞膜和细胞质中非基因组 G 蛋白偶联雌激素受体 (GPER) 的表达。这反过来又促进了 CCA 细胞的增殖和迁移。 ATZ 暴露诱导 GPER 上调，并增加 PI3K、p-PI3K、Akt、p-Akt、NF-κB 和 PCNA 的表达水平。相比之下，ATZ 治疗后，GPER 拮抗剂 G15 显着下调 GPER/PI3K/Akt/NF-κB 通路。这些结果表明 ATZ 通过 GPER/PI3K/Akt/NF-κB 通路促进 CCA 细胞增殖和迁移。此信息可以提高公众对 ATZ 污染的认识，以预防 CCA 的相对风险。版权所有 © 2024 Elsevier Inc. 保留所有权利。

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.Copyright © 2024 Elsevier Inc. All rights reserved.