Abstract
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.
Highlights
Colorectal carcinoma (CRC) is the second leading cause of cancer‐related mortality worldwide [1]
The Colo205/5‐FU cells were 29.21 times more resistant to 5‐FU compared with the Colo205 cells, and the HCT‐8/5‐FU cells were 16.04 times more resistant when compared with the HCT‐8 cells
As the CRC cell population developed with increasing MDR, LIM domain‐containing protein 1 (LIMD1) protein expression was found to significantly increase (P=0.006 and P=0.002 for LIMD1 in Colo205/5‐FU and HCT‐8/5‐FU, respectively)
Summary
Colorectal carcinoma (CRC) is the second leading cause of cancer‐related mortality worldwide [1]. Surgical intervention is no longer the only treatment option and chemotherapy presents an important strategy for the treatment of the majority of CRC patients [2]. De novo and acquired resistance to a variety of drugs is common and, the drug‐resistant phenotype of CRCs presents one of the major obstacles in its eradication [3]. Gene silencing or inhibition of associated downstream proteins is commonly used to understand gene function [4]. The aim of this study was to demonstrate that the specific silencing of LIMD1 by RNA interference may effectively reverse drug resistance in multidrug‐resistant (MDR) CRC cells by enhancing cell apoptosis, which may highlight novel investigational targets that will provide therapeutic options for CRC
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