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

被引:6
作者
Chen, Zhangxing [1 ]
Zhu, Xiaosan [1 ,2 ]
Xie, Tao [1 ]
Xie, Junpei [1 ]
Quo, Kong [3 ]
Liu, Xiang [1 ]
机构
[1] 174th Hosp PLA, Dept Gastroenterol, Xiamen 361006, Fujian, Peoples R China
[2] Xiamen Univ, Chenggong Hosp, Dept Gastroenterol, Xiamen 361003, Fujian, Peoples R China
[3] Creighton Univ, Sch Med, Ctr Clin & Translat Sci, Omaha, NE 68178 USA
关键词
apoptosis; colorectal carcinoma; multidrug resistance; LIM domain-containing protein 1; MULTIDRUG-RESISTANCE; CANCER; TRANSCRIPTION; POLYMORPHISM;
D O I
10.3892/ol.2014.2155
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
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.
引用
收藏
页码:795 / 798
页数:4
相关论文
共 13 条
[1]
Andersen V, BMC CANC, V9, P407
[2]
The multidrug resistance 1 (MDR1) gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study [J].
Andersen, Vibeke ;
Agerstjerne, Lene ;
Jensen, Dorte ;
Ostergaard, Mette ;
Saebo, Mona ;
Hamfjord, Julian ;
Kure, Elin ;
Vogel, Ulla .
BMC MEDICAL GENETICS, 2009, 10
[3]
EGFR L2 domain mutation is not correlated with resistance to cetuximab in metastatic colorectal cancer patients [J].
Ito, Yuriko ;
Yamada, Yasuhide ;
Asada, Kiyoshi ;
Ushijima, Toshikazu ;
Iwasa, Satoru ;
Kato, Ken ;
Hamaguchi, Tetsuya ;
Shimada, Yasuhiro .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2013, 139 (08) :1391-1396
[4]
Colorectal-Cancer Screening - Coming of Age [J].
Levin, Theodore R. ;
Corley, Douglas A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (12) :1164-1166
[5]
Interference Between DNA Replication and Transcription as a Cause of Genomic Instability [J].
Lin, Yea-Lih ;
Pasero, Philippe .
CURRENT GENOMICS, 2012, 13 (01) :65-73
[6]
Sorcin Induces a Drug-Resistant Phenotype in Human Colorectal Cancer by Modulating Ca2+ Homeostasis [J].
Maddalena, Francesca ;
Laudiero, Gabriella ;
Piscazzi, Annamaria ;
Secondo, Agnese ;
Scorziello, Antonella ;
Lombardi, Valentina ;
Matassa, Danilo Swann ;
Fersini, Alberto ;
Neri, Vincenzo ;
Esposito, Franca ;
Landriscina, Matteo .
CANCER RESEARCH, 2011, 71 (24) :7659-7669
[7]
A Phase I Trial of Isolated Hepatic Perfusion (IHP) Using 5-FU and Oxaliplatin in Patients with Unresectable Isolated Liver Metastases from Colorectal Cancer [J].
Magge, D. ;
Zureikat, A. H. ;
Bartlett, D. L. ;
Holtzman, M. P. ;
Choudry, H. A. ;
Beumer, J. H. ;
Pingpank, J. F. ;
Holleran, J. L. ;
Strychor, S. ;
Cunningham, D. E. ;
Jones, H. L. ;
Zeh, H. J., III .
ANNALS OF SURGICAL ONCOLOGY, 2013, 20 (07) :2180-2187
[8]
Mastalier B, 2012, J Med Life, V5, P348
[9]
Multidrug resistance protein 2 genetic polymorphism and colorectal cancer recurrence in patients receiving adjuvant FOLFOX-4 chemotherapy [J].
Mirakhorli, Mojgan ;
Rahman, Sabariah Abdul ;
Abdullah, Syahrilnizam ;
Vakili, Masoud ;
Rozafzon, Reza ;
Khoshzaban, Ahad .
MOLECULAR MEDICINE REPORTS, 2013, 7 (02) :613-617
[10]
LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p2l.3, binds pRB and represses E2F-driven transcription [J].
Sharp, TV ;
Munoz, F ;
Bourboulia, D ;
Presneau, N ;
Darai, E ;
Wang, HW ;
Cannon, M ;
Butcher, DN ;
Nicholson, AG ;
Klein, G ;
Imreh, S ;
Boshoff, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (47) :16531-16536