Bcl-2 gene silencing by RNA interference inhibits the growth of the human gallbladder carcinoma cell line GBC-SD in vitro and in vivo

被引:10
作者
Geng, Zhi-Min [1 ]
Zhang, Min [1 ]
Pan, Xiao-Tao [1 ]
Wang, Lin [1 ]
机构
[1] Xi An Jiao Tong Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Coll Med, Xian 710061, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
gallbladder carcinoma; RNA interference; B-cell lymphoma/leukemia-2 gene; growth; cell apoptosis; ASSOCIATION; EXPRESSION; APOPTOSIS; CANCER; P53;
D O I
10.3892/or.2013.2539
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gallbladder carcinoma is the most common malignant tumor in the biliary system; however, the underlying mechanisms of tumor initiation, progression and metastasis are not fully understood to date. The B-cell lymphoma/leukemia-2 (Bcl-2) gene, which is highly expressed in gallbladder carcinoma tissue, is one of the most important regulatory factors in cell apoptosis, and plays an important role in the initiation and progression of gallbladder carcinoma. In the present study, we constructed a eukaryotic expression vector of small interference RNA (siRNA) specific to the Bcl-2 gene and transfected it into GBC-SD human gallbladder carcinoma cells. We demonstrated that the constructed Bcl-2 siRNA vector effectively silenced Bcl-2 gene expression in the GBC-SD human gallbladder carcinoma cells, inhibited cell proliferation, induced cell apoptosis, increased chemotherapeutic sensitivity to 5-fluorouracil and inhibited tumor growth in vivo. Collectively, these data reveal an important contribution of Bcl-2 to gallbladder carcinoma. Thus, the use of a synthetic inhibitor of Bcl-2 may be a promising approach for the treatment of gallbladder carcinoma.
引用
收藏
页码:793 / 800
页数:8
相关论文
共 21 条
[1]  
Fjose A, 2001, Biotechnol Annu Rev, V7, P31, DOI 10.1016/S1387-2656(01)07032-6
[2]   The secrets of the Bcl-2 family [J].
Garcia-Saez, A. J. .
CELL DEATH AND DIFFERENTIATION, 2012, 19 (11) :1733-1740
[3]   Gallbladder cancer: a morphological and molecular update [J].
Goldin, Robert David ;
Carlos Roa, Juan .
HISTOPATHOLOGY, 2009, 55 (02) :218-229
[4]   Genetic alterations in gallbladder carcinoma [J].
Kuroki, T ;
Tajima, Y ;
Matsuo, K ;
Kanematsu, T .
SURGERY TODAY, 2005, 35 (02) :101-105
[5]  
Lai ECH, 2008, SURG-J R COLL SURG E, V6, P101
[6]   Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells [J].
Lima, RT ;
Martins, SM ;
Guimaraes, JE ;
Sambade, C ;
Vasconcelos, MH .
CANCER GENE THERAPY, 2004, 11 (05) :309-316
[7]   Genetic abberations in gallbladder cancer [J].
Maurya, Sanjeev K. ;
Tewari, Mallika ;
Mishra, Raghvendra R. ;
Shukla, Hari S. .
SURGICAL ONCOLOGY-OXFORD, 2012, 21 (01) :37-43
[8]   Mechanisms of gene silencing by double-stranded RNA [J].
Meister, G ;
Tuschl, T .
NATURE, 2004, 431 (7006) :343-349
[9]   Revealing the world of RNA interference [J].
Mello, CC ;
Conte, D .
NATURE, 2004, 431 (7006) :338-342
[10]  
Mikami T, 1999, CANCER, V85, P318, DOI 10.1002/(SICI)1097-0142(19990115)85:2<318::AID-CNCR8>3.0.CO