Chen Zhangxing, Zhu Xiaosan, Xie Tao, Xie Junpei, Quo Kong, Liu Xiang
Department of Gastroenterology, The 174th Hospital of the PLA, Xiamen University, Xiamen, Fujian 361003, USA.
Department of Gastroenterology, The 174th Hospital of the PLA, Xiamen University, Xiamen, Fujian 361003, USA ; Department of Gastroenterology, Chenggong Hospital, Xiamen University, Xiamen, Fujian 361003, USA.
Oncol Lett. 2014 Aug;8(2):795-798. doi: 10.3892/ol.2014.2155. Epub 2014 May 19.
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.
含LIM结构域蛋白1（LIMD1）在结直肠癌（CRC）多药耐药中的作用尚未明确。本研究旨在探讨沉默LIMD1后CRC多药耐药（MDR）细胞的化学敏感性。研究了通过在一年时间内暴露于递增剂量的5-氟尿嘧啶（5-FU）建立的MDR表型的Colo205和HCT-8细胞系。将LIMD1 siRNA构建体转染到CRC MDR细胞中，并全面测定表型效应。与各自的亲本细胞系相比，Colo205和HCT-8细胞系对5-FU的耐药性更强。此外，与亲本系相比，这两种MDR细胞类型中LIMD1的表达明显更多。稳定转染的细胞显示出不同程度的MDR表型逆转，与对照组相比，转染细胞中5-FU诱导的细胞凋亡增加。总之，靶向LIMD1的RNA干扰可能为CRC提供一种新的治疗选择。
