Chulabhorn International College of Medicine, Thammasat University, Rangsit Center, Klong Luang, Pathum Thani 12120, Thailand.
Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Rangsit Center, Klong Luang, Pathum Thani 12120, Thailand.
Asian Pac J Cancer Prev. 2022 Aug 1;23(8):2573-2581. doi: 10.31557/APJCP.2022.23.8.2573.
Cholangiocarcinoma (CCA) is a highly aggressive tumor with a greater risk of distant metastasis. A drug that prevents CCA development and spread is urgently needed. In this research, we investigated the effect of β-eudesmol on the migration and invasion and epithelial-mesenchymal transformation (EMT) of the CCA cell line.
MTT and transwell assays were used to investigate the antiproliferative activity, as well as activity on cell migration and cell invasion. Real-time PCR and western blot analysis were used to investigate the expression of EMT marker genes and proteins.
β-eudesmol was shown to exhibit potent antiproliferative activity (IC50 92.25-185.67 µM) and to significantly reduce CCA cell migration and invasion (27.3-62.7%). At both mRNA and protein levels, it significantly up-regulated the expression of epithelial marker E-cadherin (3-3.4-fold), while down-regulated the expression of mesenchymal markers-vimentin (0.6-0.8-fold) and snail-1 (0.4-0.6-fold). Furthermore, β-eudesmol inhibited PI3K and AKT phosphorylation (0.5-0.8-fold), while activating p38MAPK activity (1.2-3.6-fold).
Altogether, the anti-metastatic activity of β-eudesmol might be due to its suppressive effect on EMT via modulating the PI3K/AKT and p38MAPK signaling cascades.
胆管癌（CCA）是一种侵袭性很强的肿瘤，远处转移的风险更大。急需一种能预防 CCA 发展和扩散的药物。在这项研究中，我们研究了 β-桉叶醇对 CCA 细胞系迁移、侵袭和上皮-间充质转化（EMT）的影响。
MTT 和 Transwell 检测法用于研究增殖活性以及对细胞迁移和侵袭的活性。实时 PCR 和 Western blot 分析用于研究 EMT 标记基因和蛋白的表达。
β-桉叶醇表现出很强的增殖抑制活性（IC50 为 92.25-185.67 µM），并显著降低 CCA 细胞的迁移和侵袭（27.3-62.7%）。在 mRNA 和蛋白水平上，它显著上调上皮标记物 E-钙黏蛋白的表达（3-3.4 倍），同时下调间充质标记物-波形蛋白（0.6-0.8 倍）和 snail-1（0.4-0.6 倍）的表达。此外，β-桉叶醇抑制 PI3K 和 AKT 磷酸化（0.5-0.8 倍），同时激活 p38MAPK 活性（1.2-3.6 倍）。
总之，β-桉叶醇的抗转移活性可能是由于其通过调节 PI3K/AKT 和 p38MAPK 信号通路对 EMT 的抑制作用。
