Division of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand.
Center of Excellence in Stem Cell Research, Thammasat University, Pathumthani, 12120, Thailand.
Sci Rep. 2022 Jul 5;12(1):11341. doi: 10.1038/s41598-022-15298-0.
Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the damaged epithelial cells of the biliary tract. Previous studies have reported that the multi-potent mesenchymal stem cells (MSCs) activate a series of tumor signaling pathways by releasing several cytokines to influence tumor cell development. However, the roles and mechanisms of human chorion-derived MSCs (CH-MSCs) in cholangiocarcinoma progression have not been fully addressed. This present study aims to examine the effects of conditioned media derived from CH-MSCs (CH-CM) on CCA cell lines and investigate the respective underlying mechanism of action. For this purpose, MSCs were isolated from chorion tissue, and three cholangiocarcinoma cell lines, namely KKU100, KKU213A, and KKU213B, were used. MTT assay, annexin V/PI analysis, and JC-1 staining were used to assess the effects of CH-CM on proliferation and apoptosis of CCA cells, respectively. Moreover, the effect of CH-CM on caspase-dependent apoptotic pathways was also evaluated. The western blotting assay was also used for measuring the expression of JAK2/STAT3 signaling pathway-associated proteins. The results showed that CH-CM suppressed proliferation and promoted apoptosis of CCA cell lines. CH-CM treatment-induced loss of mitochondrial membrane potential (∆Ψm) in CCA cell lines. The factors presented in the CH-CM also inhibited JAK2/STAT3 signaling, reduced the expression of BCL-2, and increased BAX expression in CCA cells. In conclusion, our study suggests that the CH-CM has a potent anti-cancer effect on cholangiocarcinoma cells and thus provides opportunities for use in alternative cell therapy or in combination with a conventional chemotherapeutic drug to increase the efficiency of CCA treatment.
胆管癌（CCA）是一种源自胆管受损上皮细胞的侵袭性恶性肿瘤。先前的研究报道，多能间充质干细胞（MSCs）通过释放几种细胞因子激活一系列肿瘤信号通路，从而影响肿瘤细胞的发展。然而，人绒毛膜来源的间充质干细胞（CH-MSCs）在胆管癌进展中的作用和机制尚未完全阐明。本研究旨在研究 CH-MSCs 条件培养基（CH-CM）对胆管癌细胞系的影响，并探讨其各自的作用机制。为此，从绒毛膜组织中分离出 MSCs，并用三种胆管癌细胞系，即 KKU100、KKU213A 和 KKU213B 进行实验。MTT 检测、Annexin V/PI 分析和 JC-1 染色分别用于评估 CH-CM 对 CCA 细胞增殖和凋亡的影响。此外，还评估了 CH-CM 对 caspase 依赖性凋亡途径的影响。Western blot 检测也用于测量 JAK2/STAT3 信号通路相关蛋白的表达。结果表明，CH-CM 抑制了 CCA 细胞系的增殖并促进了其凋亡。CH-CM 处理诱导 CCA 细胞系中线粒体膜电位（∆Ψm）的丧失。CH-CM 中存在的因子还抑制了 JAK2/STAT3 信号通路，降低了 BCL-2 的表达，并增加了 CCA 细胞中 BAX 的表达。综上所述，本研究表明 CH-CM 对胆管癌细胞具有强大的抗癌作用，因此为替代细胞治疗或与常规化疗药物联合使用以提高 CCA 治疗效率提供了机会。
