Cisplatin-induced activation of TGF-βsignaling contributes to drug resistance
作者机构：Department of Biosciences and InformaticsFaculty of Science and TechnologyKeio UniversityYokohama223-8522Japan Department of NeurologyJuntendo University Graduate School of MedicineTokyo113-8421Japan Laboratory of BiochemistryShowa Pharmaceutical UniversityTokyo194-8543Japan
出 版 物：《Oncology Research》 (肿瘤学研究（英文）)
年 卷 期：2024年第32卷第1期
页 面：139-150页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：the Japan Society for the Promotion of Science(JSPS) KAKENHI Grant Number 26350974
主 题：Cisplatin EMT Chemo-resistance TGF-β
摘 要：Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer ***,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains *** address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell *** these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was ***,the expression of EMT-related transcription factors,including Slug,was *** the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant *** mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic ***,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene *** results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.
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