Bcl-2 gene silence enhances the sensitivity toward 5-Fluorouracil in gastric adenocarcinoma cells

被引:13
作者
Yu, Dong-feng [1 ]
Wu, Fan-rong [3 ]
Liu, Yi [1 ]
Liu, Hong [2 ]
Xia, Quan [2 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Gen Surg, Hefei, Anhui, Peoples R China
[2] Anhui Med Univ, Affiliated Hosp 1, Dept Pharm, Hefei, Anhui, Peoples R China
[3] Anhui Med Univ, Sch Pharm, Hefei, Anhui, Peoples R China
关键词
Small interfering RNA (siRNA); Bcl-2; Gastric adenocarcinoma cell; Apoptosis; 5-Fluorouracil;
D O I
10.1016/j.biopha.2013.03.007
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Because of increased insensitivity or resistance to chemical treatment in tumor patients, specific apoptotic gene silence may provide a rational approach for the development of novel therapeutic strategies. This study was to investigate whether downregulation of Bcl-2 expression by small interfering RNA (siRNA) against the Bcl-2 gene would enhance the apoptosis and sensitivity of gastric adenocarcinoma SGC-7901 cell to 5-Fluorouracil. Transfections of SGC-7901 cells with siRNA were performed using cationic liposomes. Sequence-specific downregulation of Bcl-2 expression was measured by RT-PCR and Western blot analysis. Cell proliferation assay was determined by MTT assay and apoptotic cell rates were determined by flow cytometry assay. Results showed that the siRNA could downregulate Bcl-2 expression, which increased apoptosis and sensitivity of SGC-7901 cell to 5Fluorouracil (P < 0.05). This study indicated that inhibition of Bcl-2 expression by siRNA would be useful a new useful protocol to increase the effect of 5-Fluorouracil on treatment of gastric adenocarcinoma, which may play an important role in developing novel therapeutic strategies in the future. (C) 2013 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:615 / 619
页数:5
相关论文
共 18 条
[1]   Apoptosis pathways in cancer and cancer therapy [J].
Debatin, KM .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2004, 53 (03) :153-159
[2]  
Jemal A, 2011, CA-CANCER J CLIN, V61, P134, DOI [10.3322/caac.20115, 10.3322/caac.20107, 10.3322/caac.21492]
[3]   The Intrinsic Apoptosis Pathways as a Target in Anticancer Therapy [J].
Jendrossek, Verena .
CURRENT PHARMACEUTICAL BIOTECHNOLOGY, 2012, 13 (08) :1426-1438
[4]   Shooting at survivors: Bcl-2 family members as drug targets for cancer [J].
Juin, P ;
Geneste, O ;
Raimbaud, E ;
Hickman, JA .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2004, 1644 (2-3) :251-260
[5]   Strategies for silencing human disease using RNA interference [J].
Kim, Daniel H. ;
Rossi, John J. .
NATURE REVIEWS GENETICS, 2007, 8 (03) :173-184
[6]  
Krajewska M, 1996, AM J PATHOL, V149, P1449
[7]   Bcl-2-family proteins and the role of mitochondria in apoptosis [J].
Kuwana, T ;
Newmeyer, DD .
CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (06) :691-699
[8]   Clinical overview: adjuvant therapy of gastrointestinal cancer [J].
Macdonald, JS .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2004, 54 (Suppl 1) :S4-S11
[9]   Gene silencing in mammals by small interfering RNAs [J].
McManus, MT ;
Sharp, PA .
NATURE REVIEWS GENETICS, 2002, 3 (10) :737-747
[10]   CANCER CHEMOPREVENTION - PRINCIPLES AND PROSPECTS [J].
MORSE, MA ;
STONER, GD .
CARCINOGENESIS, 1993, 14 (09) :1737-1746