Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Medical Sciences Program, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Pestic Biochem Physiol. 2024 Aug;203:105988. doi: 10.1016/j.pestbp.2024.105988. Epub 2024 Jun 13.
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.
莠去津（ATZ）是一种在全球范围内广泛分布的除草剂，在环境暴露时可能会对各种癌症的发展产生潜在风险。然而，ATZ 对胆管癌（CCA）的作用和分子机制尚不清楚。本研究旨在探讨 ATZ 对体外 CCA 细胞增殖和迁移的影响。永生化人胆管细胞（MMNK-1）和三种 CCA 细胞系（KKU-055、KKU-100 和 KKU-213B）用 0.01 至 100 μM 的 ATZ 和 17β-雌二醇（E2）处理。结果表明，与 E2 相似，低剂量（0.01 至 1 μM）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非基因组 G 蛋白偶联雌激素受体（GPER）的表达，从而促进了 CCA 细胞的增殖和迁移。ATZ 暴露诱导 GPER 上调，并增加了 PI3K、p-PI3K、Akt、p-Akt、NF-κB 和 PCNA 的表达水平。相反，在用 ATZ 处理后，GPER 拮抗剂 G15 显著下调了 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 细胞的增殖和迁移。这些信息可以增强公众对 ATZ 污染的认识，以预防 CCA 的相对风险。
