Monika Cuprych-Belter, Agnieszka Łupicka-Słowik, Artur Anisiewicz, Martin Michaelis, Jindrich Cinatl, Mateusz Psurski
{"title":"一组化疗耐药膀胱癌细胞系对顺铂、长春碱和吉西他滨的不同适应策略","authors":"Monika Cuprych-Belter, Agnieszka Łupicka-Słowik, Artur Anisiewicz, Martin Michaelis, Jindrich Cinatl, Mateusz Psurski","doi":"10.20517/cdr.2025.95","DOIUrl":null,"url":null,"abstract":"<p><p><b>Aim:</b> Urinary bladder cancer (UBC) often develops chemoresistance, reducing treatment effectiveness. This study aimed to investigate diverse molecular mechanisms underlying acquired resistance by establishing and characterizing a comprehensive panel of UBC cell lines resistant to common chemotherapeutics. <b>Methods:</b> Fifteen UBC cell lines were examined: three parental lines (RT-112, TCC-SUP, UMUC-3) and twelve derived sublines adapted to cisplatin, vinblastine, or gemcitabine. Drug sensitivity was assessed using the SRB assay. Resistance mechanisms were explored via quantitative real-time PCR (targeting genes including <i>ABCB1</i>, <i>dCK</i>, <i>hENT1</i>, <i>ECHDC1</i>, <i>TUBB3</i>), Western blotting (assessing proteins such as p21, Cyclin B, and Mcl-1), and biochemical assessment of glutathione levels and redox state. <b>Results:</b> The adapted sublines exhibited distinct resistance profiles and cross-resistance patterns. Gene expression and protein analyses revealed drug- and lineage-specific alterations, involving factors such as p21, Cyclin B, and Mcl-1. Changes in glutathione metabolism were also associated with resistance. Notably, no single, universal mechanism accounted for resistance across the entire panel. <b>Conclusion:</b> UBC cells develop diverse, context-dependent adaptive strategies to resist cisplatin, vinblastine, and gemcitabine. These findings highlight the complexity of chemoresistance mechanisms. The characterized cell line panel represents a valuable resource for future studies aimed at understanding and overcoming drug resistance in bladder cancer, suggesting that personalized therapeutic approaches may be necessary.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"8 ","pages":"49"},"PeriodicalIF":4.6000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462402/pdf/","citationCount":"0","resultStr":"{\"title\":\"Distinct adaptive strategies to cisplatin, vinblastine and gemcitabine in a panel of chemoresistant bladder cancer cell lines.\",\"authors\":\"Monika Cuprych-Belter, Agnieszka Łupicka-Słowik, Artur Anisiewicz, Martin Michaelis, Jindrich Cinatl, Mateusz Psurski\",\"doi\":\"10.20517/cdr.2025.95\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Aim:</b> Urinary bladder cancer (UBC) often develops chemoresistance, reducing treatment effectiveness. This study aimed to investigate diverse molecular mechanisms underlying acquired resistance by establishing and characterizing a comprehensive panel of UBC cell lines resistant to common chemotherapeutics. <b>Methods:</b> Fifteen UBC cell lines were examined: three parental lines (RT-112, TCC-SUP, UMUC-3) and twelve derived sublines adapted to cisplatin, vinblastine, or gemcitabine. Drug sensitivity was assessed using the SRB assay. Resistance mechanisms were explored via quantitative real-time PCR (targeting genes including <i>ABCB1</i>, <i>dCK</i>, <i>hENT1</i>, <i>ECHDC1</i>, <i>TUBB3</i>), Western blotting (assessing proteins such as p21, Cyclin B, and Mcl-1), and biochemical assessment of glutathione levels and redox state. <b>Results:</b> The adapted sublines exhibited distinct resistance profiles and cross-resistance patterns. Gene expression and protein analyses revealed drug- and lineage-specific alterations, involving factors such as p21, Cyclin B, and Mcl-1. Changes in glutathione metabolism were also associated with resistance. Notably, no single, universal mechanism accounted for resistance across the entire panel. <b>Conclusion:</b> UBC cells develop diverse, context-dependent adaptive strategies to resist cisplatin, vinblastine, and gemcitabine. These findings highlight the complexity of chemoresistance mechanisms. The characterized cell line panel represents a valuable resource for future studies aimed at understanding and overcoming drug resistance in bladder cancer, suggesting that personalized therapeutic approaches may be necessary.</p>\",\"PeriodicalId\":70759,\"journal\":{\"name\":\"癌症耐药(英文)\",\"volume\":\"8 \",\"pages\":\"49\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462402/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"癌症耐药(英文)\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.20517/cdr.2025.95\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"癌症耐药(英文)","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.20517/cdr.2025.95","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Distinct adaptive strategies to cisplatin, vinblastine and gemcitabine in a panel of chemoresistant bladder cancer cell lines.
Aim: Urinary bladder cancer (UBC) often develops chemoresistance, reducing treatment effectiveness. This study aimed to investigate diverse molecular mechanisms underlying acquired resistance by establishing and characterizing a comprehensive panel of UBC cell lines resistant to common chemotherapeutics. Methods: Fifteen UBC cell lines were examined: three parental lines (RT-112, TCC-SUP, UMUC-3) and twelve derived sublines adapted to cisplatin, vinblastine, or gemcitabine. Drug sensitivity was assessed using the SRB assay. Resistance mechanisms were explored via quantitative real-time PCR (targeting genes including ABCB1, dCK, hENT1, ECHDC1, TUBB3), Western blotting (assessing proteins such as p21, Cyclin B, and Mcl-1), and biochemical assessment of glutathione levels and redox state. Results: The adapted sublines exhibited distinct resistance profiles and cross-resistance patterns. Gene expression and protein analyses revealed drug- and lineage-specific alterations, involving factors such as p21, Cyclin B, and Mcl-1. Changes in glutathione metabolism were also associated with resistance. Notably, no single, universal mechanism accounted for resistance across the entire panel. Conclusion: UBC cells develop diverse, context-dependent adaptive strategies to resist cisplatin, vinblastine, and gemcitabine. These findings highlight the complexity of chemoresistance mechanisms. The characterized cell line panel represents a valuable resource for future studies aimed at understanding and overcoming drug resistance in bladder cancer, suggesting that personalized therapeutic approaches may be necessary.