Oncolytic adenovirus-mediated shRNA against Apollon inhibits tumor cell growth and enhances antitumor effect of 5-fluorouracil

被引：48
作者：
Chu, L. [1 ]
Gu, J. [1 ]
Sun, L. [1 ]
Qian, Q. [2 ]
Qian, C. [2 ]
Liu, X. [1 ,2 ]
机构：
[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China
[2] Zhejiang Sci Tech Univ, Xinyuan Inst Med & Biotechnol, Hangzhou, Peoples R China
来源：
GENE THERAPY | 2008年 / 15卷 / 07期
基金：
中国国家自然科学基金;
关键词：
oncolytic adenovirus; short hairpin RNA; Apollon; cancer therapy; 5-fluorouracil;
D O I：
10.1038/gt.2008.6
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Apollon, a membrane-associated inhibitor of apoptosis protein, protects cells against apoptosis and is upregulated in certain tumor cells. In this study, the effects of Apollon protein knockdown by RNA interference on the growth of human HeLa, HT-1080 and MCF-7 cells in vitro and in vivo were investigated. An oncolytic adenovirus (ZD55) containing the RNA polymerase III-dependent U6 promoter to express short hairpin RNA (shRNA) directed against Apollon (ZD55-siApollon) was constructed. Our data show that ZD55-siApollon successfully exerts a gene knockdown effect and causes the inhibition of tumor cell growth both in culture and in athymic mice in vivo. Cell cycle analysis, 4',6-diamidino-2-phenylindole staining and western blot analysis reveal that ZD55-siApollon-mediated suppression of Apollon induces apoptosis. Intratumoral injection of ZD55-siApollon significantly inhibits tumor growth in HT-1080 xenograft mice. Furthermore, ZD55-siApollon enhances the antitumor effect of 5-fluorouracil, a chemotherapeutic agent. In conclusion, these results suggest that the depletion of Apollon by oncolytic adenovirus-shRNA delivery system provides a promising method for cancer therapy.
引用
收藏
页码：484 / 494
页数：11
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