Induced apoptosis with ultrasound-mediated microbubble destruction and shRNA targeting survivin in transplanted tumors

被引:25
作者
Chen, Zhi-Yi [1 ]
Liang, Kun [2 ]
Xie, Ming-Xing [3 ]
Wang, Xin-Fang [3 ]
Lue, Qing [3 ]
Zhang, Jing [3 ]
机构
[1] Third Affiliated Hosp, Dept Med Ultrasound, Guangzhou Med Coll, Guangzhou 510150, Guangdong, Peoples R China
[2] Third Affiliated Hosp, Dept Gynecol & Obstet, Guangzhou Med Coll, Guangzhou 510150, Guangdong, Peoples R China
[3] Huazhong Univ Sci & Technol, Dept Ultrasonog, Union Hosp, Tongji Med Coll,Hubei Prov Key Lab Mol Imaging, Wuhan 430074, Peoples R China
关键词
apoptosis; gene transfer techniques; microbubble; non-viral; RNA interference; survivin; ultrasound; INTENSITY FOCUSED ULTRASOUND; RNA INTERFERENCE; GENE-THERAPY; HELA-CELLS; CANCER; EXPRESSION; TRANSFECTION; PROGRESSION; ACTIVATION; VECTORS;
D O I
10.1007/s12325-008-0129-4
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
Introduction: This study was designed to evaluate the consequences of survivin down-modulation on tumor growth in a nude mice model combined with short hairpin RNA recombinant vector (shRNA) and ultrasound-mediated microbubble destruction (UMMD). Methods: BALB/c nude mice were inoculated subcutaneously with cervical cancer cells (HeLa) and tumors (5-10 mm) developed. A shRNA recombinant vector that targeted the survivin gene (survivin-shRNA) was constructed. The mice were divided into three groups (n=6 in each group) and injected with survivin-shRNA: plasmid group (P), plasmid+ultrasound exposure group (P+US), and plasmid+microbubble (SonoVueA (R))+ultrasound group (P+UMMD). Protein expression of survivin, proliferating cell nuclear antigen (PCNA), and caspase-3 were investigated by immunohistochemistry, and proliferation index (PI) and apoptotic index (AI) were measured. Results: The protein expression of survivin and PCNA was markedly downregulated, while caspase-3 was markedly upregulated in the P+UMMD group as compared with that of the P group and P+US group. PI decreased significantly (P < 0.05), whereas AI increased remarkably (P < 0.01) in the P+UMMD group as compared with that of the P group and P+US group. These data indicate that the combined strategy of UMMD and survivin-shRNA effectively induces silencing of the survivin gene, resulting in inhibition of proliferation and induction of apoptosis in nude mice. Conclusions: Survivin could be regarded as an ideal target for anticancer intervention of cervical cancer. The combination of shRNA and UMMD could enhance antitumor efficacy as a result of synergism. This may be a powerful, promising non-viral technology that could be used in tumor gene therapy.
引用
收藏
页码:99 / 106
页数:8
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