Pub Date : 2018-06-26DOI: 10.31491/CSRC.2018.6.015
Hong-rui Zhang, Yan Zhang, Fu-lian Qu, Zhiqiao Xu, Pei-jie Liu
Objective: The aim of this study was to explore the potential involvement of the miR-493-5p/BRCA1 pathway in the anti-cell drug resistance activity of artesunate in lung carcinomas. Method: Two drug-resistant lung carcinoma cell lines, A549 and SBC-3, resistant to cisplatin (DDP) and adriamycin (ADM), respectively, and their parental cell lines (A549 and SBC-3) were used in this study. Cell viability was determined by an MTT assay. The relative expression of miR-493-5p and BRCA1 mRNA was analyzed by quantitative real-time PCR. The protein expression of BRCA1, breast cancer resistance protein (BCRP), and (p)PI3K/AKT was determined by a Western blot. Results: Artesunate attenuated the viability of A549/DDP and SBC-3/ADM cells and suppressed the expression of BCRP, an important multidrug resistance protein in lung carcinoma cells, accompanied by upregulation of miR-493-5p and downregulation of BRCA1. In artesunate-treated A549/DDP and SBC-3/ADM cells, miR-493-5p silencing reversed the anti-cell drug resistance activity of artesunate and resulted in increased cell viability and BRCP expression. Simultaneously, miR-493-5p silencing contributed to BRCA1 upregulation and phosphorylation of PI3K and AKT. As shown by a luciferase reporter gene assay, BRCA1 was a target gene for miR-493-5p, and its expression was negatively regulated by miR-493-5p. miR-493-5p silencing reversed the anticell drug resistance activity of artesunate, and this finding was further supported by a murine tumor-bearing model. Conclusion: The data support the anti-cell drug resistance activity of artesunate in lung carcinoma cells and sheds light on the role of the miR-493-5p/BRCA1 pathway in this process.
{"title":"Artesunate Improves Drug Resistance of Lung Carcinomas Via Regulation of MiR-493-5p","authors":"Hong-rui Zhang, Yan Zhang, Fu-lian Qu, Zhiqiao Xu, Pei-jie Liu","doi":"10.31491/CSRC.2018.6.015","DOIUrl":"https://doi.org/10.31491/CSRC.2018.6.015","url":null,"abstract":"Objective: The aim of this study was to explore the potential involvement of the miR-493-5p/BRCA1 pathway in the anti-cell drug resistance activity of artesunate in lung carcinomas. Method: Two drug-resistant lung carcinoma cell lines, A549 and SBC-3, resistant to cisplatin (DDP) and adriamycin (ADM), respectively, and their parental cell lines (A549 and SBC-3) were used in this study. Cell viability was determined by an MTT assay. The relative expression of miR-493-5p and BRCA1 mRNA was analyzed by quantitative real-time PCR. The protein expression of BRCA1, breast cancer resistance protein (BCRP), and (p)PI3K/AKT was determined by a Western blot. Results: Artesunate attenuated the viability of A549/DDP and SBC-3/ADM cells and suppressed the expression of BCRP, an important multidrug resistance protein in lung carcinoma cells, accompanied by upregulation of miR-493-5p and downregulation of BRCA1. In artesunate-treated A549/DDP and SBC-3/ADM cells, miR-493-5p silencing reversed the anti-cell drug resistance activity of artesunate and resulted in increased cell viability and BRCP expression. Simultaneously, miR-493-5p silencing contributed to BRCA1 upregulation and phosphorylation of PI3K and AKT. As shown by a luciferase reporter gene assay, BRCA1 was a target gene for miR-493-5p, and its expression was negatively regulated by miR-493-5p. miR-493-5p silencing reversed the anticell drug resistance activity of artesunate, and this finding was further supported by a murine tumor-bearing model. Conclusion: The data support the anti-cell drug resistance activity of artesunate in lung carcinoma cells and sheds light on the role of the miR-493-5p/BRCA1 pathway in this process.","PeriodicalId":158678,"journal":{"name":"Clinical Surgery Research Communications","volume":"331 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133244603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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