Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines
Abstract 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 t...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15298-0 |
| _version_ | 1811224082379702272 |
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| author | Tanachapa Jantalika Sirikul Manochantr Pakpoom Kheolamai Duangrat Tantikanlayaporn Weerachai Saijuntha Somchai Pinlaor Arthit Chairoungdua Luminita Paraoan Chairat Tantrawatpan |
| author_facet | Tanachapa Jantalika Sirikul Manochantr Pakpoom Kheolamai Duangrat Tantikanlayaporn Weerachai Saijuntha Somchai Pinlaor Arthit Chairoungdua Luminita Paraoan Chairat Tantrawatpan |
| author_sort | Tanachapa Jantalika |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T08:44:02Z |
| format | Article |
| id | doaj.art-8c6589b8a5954f88a9f86359a308cde8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T08:44:02Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8c6589b8a5954f88a9f86359a308cde82022-12-22T03:39:46ZengNature PortfolioScientific Reports2045-23222022-07-0112111210.1038/s41598-022-15298-0Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell linesTanachapa Jantalika0Sirikul Manochantr1Pakpoom Kheolamai2Duangrat Tantikanlayaporn3Weerachai Saijuntha4Somchai Pinlaor5Arthit Chairoungdua6Luminita Paraoan7Chairat Tantrawatpan8Division of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityBiodiversity and Conservation Research Unit, Walai Rukhavej Botanical Research Institute (WRBRI), Mahasarakham UniversityDepartment of Parasitology, Faculty of Medicine, Khon Kaen UniversityDepartment of Physiology, Faculty of Science, Mahidol UniversityDepartment of Biology, Faculty of Arts and Sciences, Edge Hill UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityAbstract 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.https://doi.org/10.1038/s41598-022-15298-0 |
| spellingShingle | Tanachapa Jantalika Sirikul Manochantr Pakpoom Kheolamai Duangrat Tantikanlayaporn Weerachai Saijuntha Somchai Pinlaor Arthit Chairoungdua Luminita Paraoan Chairat Tantrawatpan Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines Scientific Reports |
| title | Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines |
| title_full | Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines |
| title_fullStr | Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines |
| title_full_unstemmed | Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines |
| title_short | Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines |
| title_sort | human chorion derived mesenchymal stem cells suppress jak2 stat3 signaling and induce apoptosis of cholangiocarcinoma cell lines |
| url | https://doi.org/10.1038/s41598-022-15298-0 |
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