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Drug resistance reversed by silencing LIM domain-containing protein 1 expression in colorectal carcinoma

机译:沉默包含LIM域的蛋白1表达可逆转大肠癌的耐药性

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摘要

The role of LIM domain-containing protein 1 (LIMD1) in the multidrug resistance of colorectal carcinoma (CRC) has not yet been established. The aim of the current study was to investigate the chemosensitivity of CRC multidrug-resistant (MDR) cells following the silencing of LIMD1. The MDR phenotypic Colo205 and HCT-8 cell lines were examined, which were established by exposure to increasing doses of 5-fluorouracil (5-FU) over a period of one year. LIMD1 siRNA constructs were transfected into CRC MDR cells and the phenotypic effects were determined comprehensively. The Colo205 and HCT-8 cell lines were more resistant to 5-FU compared with their respective parental cell lines. In addition, the two MDR cell types expressed significantly more LIMD1 compared with their parental lines. The stably transfected cells showed various degrees of reversal of the MDR phenotype, and 5-FU-induced apoptosis was increased in the transfected cells compared with the controls. In conclusion, RNA interference targeting LIMD1 may present a novel therapeutic option for CRC.
机译:尚未确定含LIM域的蛋白1(LIMD1)在大肠癌(CRC)的多药耐药性中的作用。本研究的目的是研究LIMD1沉默后对CRC多药耐药(MDR)细胞的化学敏感性。检查了MDR表型Colo205和HCT-8细胞系,这些细胞系是通过在一年内暴露于增加剂量的5-氟尿嘧啶(5-FU)而建立的。将LIMD1 siRNA构建体转染到CRC MDR细胞中,全面确定其表型效应。与各自的亲本细胞系相比,Colo205和HCT-8细胞系对5-FU的耐药性更高。此外,与它们的亲本系相比,两种MDR细胞类型表达的LIMD1明显更多。稳定转染的细胞表现出不同程度的MDR表型逆转,与对照组相比,转染的细胞中5-FU诱导的细胞凋亡增加。总之,靶向LIMD1的RNA干扰可能为CRC提出新的治疗选择。

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