Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathway
Introduction Lung cancer is the leading cause of cancer-associated mortality globally. In particular, non-small cell lung cancer (NSCLC) constitutes the largest percentage of all cases of lung cancer. In clinical practice, radioresistance contributes to poor responses to radiotherapy. Therefore, the...
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Termedia Publishing House
2023-01-01
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| Series: | Archives of Medical Science |
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| Online Access: | https://www.archivesofmedicalscience.com/Oxymatrine-inhibits-the-development-of-radioresistance-in-NSCLC-cells-by-reversing,158533,0,2.html |
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| _version_ | 1832584795068039168 |
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| author | Jianming Tang Yu Cao Hong Zhang Rui Wang |
| author_facet | Jianming Tang Yu Cao Hong Zhang Rui Wang |
| author_sort | Jianming Tang |
| collection | DOAJ |
| description | Introduction
Lung cancer is the leading cause of cancer-associated mortality globally. In particular, non-small cell lung cancer (NSCLC) constitutes the largest percentage of all cases of lung cancer. In clinical practice, radioresistance contributes to poor responses to radiotherapy. Therefore, the demand remains to explore potential novel and effective mechanism underlying radioresistance to improve the efficacy of radiotherapy for NSCLC.
Material and methods
Western blotting was conducted to quantify the protein expression of epithelial-mesenchymal transition markers E-cadherin and vimentin in the A549 cell line. The proliferation of A549 cells was measured using the Cell Counting Kit-8 and colony forming assays. In addition, the apoptosis of A549 cells was analyzed by flow cytometry. Invasion and migration by NSCLC cells were quantified using Transwell and wound healing assays. Plasmids were used to overexpress decoy receptor 3 (DcR3) in A549 cells. Xenograft models were established to measure the extent of NSCLC tumor growth in vivo.
Results
Our study clarified the activation of the DcR3/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK-3β) pathway in radioresistant NSCLC cells. Oxymatrine (OMT) treatment restored radiosensitivity and inhibited irradiation-induced epithelial-mesenchymal transition (EMT), invasion and migration in NSCLC cells through the DcR3/AKT/GSK-3β pathway in vitro. By contrast, OMT treatment promoted the suppressive effects of radiation on the weight and volume of the xenograft tumors in animal models.
Conclusions
OMT suppressed the development of radioresistance in NSCLC cells by promoting radiosensitivity, through the reversal of EMT process by inhibiting the DcR3/AKT/GSK-3β pathway. |
| format | Article |
| id | doaj-art-72f26cb305824d43931f82067f72ced3 |
| institution | Kabale University |
| issn | 1734-1922 1896-9151 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Termedia Publishing House |
| record_format | Article |
| series | Archives of Medical Science |
| spelling | doaj-art-72f26cb305824d43931f82067f72ced32025-01-27T10:44:31ZengTermedia Publishing HouseArchives of Medical Science1734-19221896-91512023-01-012051631165410.5114/aoms/158533158533Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathwayJianming Tang0Yu Cao1Hong Zhang2Rui Wang3The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaThe Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaThe Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaThe Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaIntroduction Lung cancer is the leading cause of cancer-associated mortality globally. In particular, non-small cell lung cancer (NSCLC) constitutes the largest percentage of all cases of lung cancer. In clinical practice, radioresistance contributes to poor responses to radiotherapy. Therefore, the demand remains to explore potential novel and effective mechanism underlying radioresistance to improve the efficacy of radiotherapy for NSCLC. Material and methods Western blotting was conducted to quantify the protein expression of epithelial-mesenchymal transition markers E-cadherin and vimentin in the A549 cell line. The proliferation of A549 cells was measured using the Cell Counting Kit-8 and colony forming assays. In addition, the apoptosis of A549 cells was analyzed by flow cytometry. Invasion and migration by NSCLC cells were quantified using Transwell and wound healing assays. Plasmids were used to overexpress decoy receptor 3 (DcR3) in A549 cells. Xenograft models were established to measure the extent of NSCLC tumor growth in vivo. Results Our study clarified the activation of the DcR3/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK-3β) pathway in radioresistant NSCLC cells. Oxymatrine (OMT) treatment restored radiosensitivity and inhibited irradiation-induced epithelial-mesenchymal transition (EMT), invasion and migration in NSCLC cells through the DcR3/AKT/GSK-3β pathway in vitro. By contrast, OMT treatment promoted the suppressive effects of radiation on the weight and volume of the xenograft tumors in animal models. Conclusions OMT suppressed the development of radioresistance in NSCLC cells by promoting radiosensitivity, through the reversal of EMT process by inhibiting the DcR3/AKT/GSK-3β pathway.https://www.archivesofmedicalscience.com/Oxymatrine-inhibits-the-development-of-radioresistance-in-NSCLC-cells-by-reversing,158533,0,2.htmlnon-small cell lung canceroxymatrineinvasionmigrationa549 cellxenograft |
| spellingShingle | Jianming Tang Yu Cao Hong Zhang Rui Wang Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathway Archives of Medical Science non-small cell lung cancer oxymatrine invasion migration a549 cell xenograft |
| title | Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathway |
| title_full | Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathway |
| title_fullStr | Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathway |
| title_full_unstemmed | Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathway |
| title_short | Oxymatrine inhibits the development of radioresistance in NSCLC cells by reversing EMT through the DcR3/AKT/GSK-3β pathway |
| title_sort | oxymatrine inhibits the development of radioresistance in nsclc cells by reversing emt through the dcr3 akt gsk 3β pathway |
| topic | non-small cell lung cancer oxymatrine invasion migration a549 cell xenograft |
| url | https://www.archivesofmedicalscience.com/Oxymatrine-inhibits-the-development-of-radioresistance-in-NSCLC-cells-by-reversing,158533,0,2.html |
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