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  • Title: Induced apoptosis with ultrasound-mediated microbubble destruction and shRNA targeting survivin in transplanted tumors.
    Author: Chen ZY, Liang K, Xie MX, Wang XF, Lü Q, Zhang J.
    Journal: Adv Ther; 2009 Jan; 26(1):99-106. PubMed ID: 19083158.
    Abstract:
    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 (SonoVue(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.
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