Suppressing the growth of rectal cancer xenografts derived from patient tumors by an adenovector expressing small hairpin RNA targeting Bcl-XL

被引:5
|
作者
Zhu, Hongbo [1 ,2 ]
Zhou, Wei [1 ,2 ]
Hu, Jingzi [3 ]
Huang, Zhongting [2 ]
Lao, Weifeng [1 ]
Huang, Xuefeng [1 ]
He, Chao [1 ,2 ]
机构
[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Colorectal Surg, Sch Med, Hangzhou 310016, Zhejiang, Peoples R China
[2] Zhejiang Univ, Key Lab Biotherapy Zhejiang Prov, Sir Run Run Shaw Hosp, Sch Med, Hangzhou 310016, Zhejiang, Peoples R China
[3] Aviat Med Evaluat & Training Ctr Airforce Hangzho, Dept Internal Med, Hangzhou, Zhejiang, Peoples R China
来源
JOURNAL OF GENE MEDICINE | 2012年 / 14卷 / 12期
基金
中国国家自然科学基金;
关键词
adenovirus; Bcl-XL; rectal cancer; small hairpin RNA; xenograft; COLON-CANCER; COLORECTAL-CANCER; IMMUNODEFICIENT MICE; ACQUIRED-RESISTANCE; INDUCED APOPTOSIS; CELL-LINES; 5-FLUOROURACIL; BCL-X(L); TRAIL; MOUSE;
D O I
10.1002/jgm.2681
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background Bcl-XL, a mitochondria membrane protein, is overexpressed in colorectal cancers and promotes cell survival. We have previously shown that the adenovector expressing small hairpin (sh)RNA targeting Bcl-XL could induce significantly apoptosis in colon cancer cells. In the present study, we aimed to further detect the anti-cancer effect of adenovector expressing the shRNA targeting Bcl-XL (Ad/Bcl-XL shRNA) on rectal cancer xenografts that were derived from patient tumors. Methods We first established three rectal cancer xenografts. These xenografts were subsequently treated with Ad/Bcl-XL shRNA alone or in combination with 5-fluouracil (5-Fu). Finally, the inhibition of tumor growth, survival time and induction of apoptosis were analyzed. Results The results obtained demonstrated that Ad/Bcl-XL shRNA could effectively suppress the tumor growth of all three rectal cancer xenografts and prolong their survival time. After being combined with 5-Fu, the suppressing effect of Ad/Bcl-XL shRNA was enhanced further. In addition, the data also showed that Ad/Bcl-XL shRNA combined with 5-Fu could significantly increase the apoptotic ratio in the rectal cancer xenograft. Conclusions These data indicate that Ad/Bcl-XL shRNA with or without 5-Fu has effective anti-tumor effects on the patient tumor-derived rectal cancer xenografts, suggesting that it could be a potential strategy for rectal cancer therapy. Copyright (C) 2012 John Wiley & Sons, Ltd.
引用
收藏
页码:761 / 768
页数:8
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