RNA interference targeting HBx suppresses tumor growth and enhances cisplatin chemosensitivity in human hepatocellular carcinoma

被引:75
作者
Cheng, Alfred S. L.
Wong, Nathalie
Tse, Ada M. Y.
Chan, Kathy Y. Y.
Chan, Kai K.
Sung, Joseph J. Y.
Chan, Henry L. Y.
机构
[1] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Dept Anatom & Cellular Pathol, Shatin, Hong Kong, Peoples R China
关键词
HBx; RNAi; cisplatin; chemosensitivity; hepatocellular carcinoma;
D O I
10.1016/j.canlet.2007.01.004
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The X protein of hepatitis B virus (HBx) is often expressed in human hepatocellular carcinoma (HCC) but its role on tumor growth is not fully clarified. In this study, RNA interference was employed to knockdown HBx expression in Hep3B HCC cells, which naturally express carboxyl-end truncated form of HBx frequently found in HCC tissues. Specific knockdown of HBx strongly inhibited cell growth and tumorigenicity in xenograft model. HBx repression induced apoptosis in Hep3B cells and significantly increased cell sensitivity to cisplatin-induced apoptosis. These results suggest that RNA interference-mediated HBx suppression exerts potent anti-proliferative and chemosensitizing effects in human HCC. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:43 / 52
页数:10
相关论文
共 38 条
[1]
Dual effects of hepatitis B virus X protein on the regulation of cell-cycle control depending on the status of cellular p53 [J].
Ahn, JY ;
Jung, EY ;
Kwun, HJ ;
Lee, CW ;
Sung, YC ;
Jang, KL .
JOURNAL OF GENERAL VIROLOGY, 2002, 83 :2765-2772
[2]
High prevalence of 1762T 1764A mutations in the basic core promoter of hepatitis B virus isolated from black Africans with hepatocellular carcinoma compared with asymptomatic carriers [J].
Baptista, M ;
Kramvis, A ;
Kew, MC .
HEPATOLOGY, 1999, 29 (03) :946-953
[3]
The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines [J].
Bergametti, F ;
Prigent, S ;
Luber, B ;
Benoit, A ;
Tiollais, P ;
Sarasin, A ;
Transy, C .
ONCOGENE, 1999, 18 (18) :2860-2871
[4]
Stable suppression of tumorigenicity by virus-mediated RNA interference [J].
Brummelkamp, TR ;
Bernards, R ;
Agami, R .
CANCER CELL, 2002, 2 (03) :243-247
[5]
Hepatocellular carcinoma: Current management and future trends [J].
Carr, BI .
GASTROENTEROLOGY, 2004, 127 (05) :S218-S224
[6]
Knock-down of hepatitis B virus X protein reduces the tumorigenicity of hepatocellular carcinoma cells [J].
Chan, DW ;
Ng, IOL .
JOURNAL OF PATHOLOGY, 2006, 208 (03) :372-380
[7]
Expression of integrated hepatitis B virus X variants in human hepatocellular carcinomas and its significance [J].
Chen, WN ;
Oon, CJ ;
Leong, AL ;
Koh, S ;
Teng, SW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 276 (03) :885-892
[8]
Expression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: implication of HBx in upregulation of COX-2 [J].
Cheng, ASL ;
Chan, HLY ;
Leung, WK ;
To, KF ;
Go, MYY ;
Chan, JYH ;
Liew, CT ;
Sung, JJY .
MODERN PATHOLOGY, 2004, 17 (10) :1169-1179
[9]
Hot-spot mutations in hepatitis B virus X gene in hepatocellular carcinoma [J].
Chu, CHC ;
Hao, YW ;
Tabor, E .
LANCET, 1996, 348 (9027) :625-626
[10]
Chung TW, 2004, FASEB J, V18, P1123, DOI 10.1096/fj.03-1429fje