Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines

• Published in: Scientific reports Vol. 12; no. 1; p. 11341
• Main Authors: Jantalika, Tanachapa, Manochantr, Sirikul, Kheolamai, Pakpoom, Tantikanlayaporn, Duangrat, Saijuntha, Weerachai, Pinlaor, Somchai, Chairoungdua, Arthit, Paraoan, Luminita, Tantrawatpan, Chairat
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.07.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/532; 631/67; 631/80; Annexin V; Antitumor activity; Apoptosis; BAX protein; Bcl-2 protein; Biliary tract; Caspase; Cell proliferation; Cell therapy; Cholangiocarcinoma; Chorion; Cytokines; Epithelial cells; Humanities and Social Sciences; Janus kinase 2; Malignancy; Membrane potential; Mesenchymal stem cells; Mitochondria; multidisciplinary; Science; Science (multidisciplinary); Signal transduction; Stat3 protein; Stem cells; Tumors; Western blotting
• ISSN: 2045-2322; 2045-2322
• 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.