Induced apoptosis with ultrasound-mediated microbubble destruction and shRNA targeting survivin in transplanted tumors
Source: Advances in Therapy, Volume 26, Number 1, January 2009 , pp. 99-106(8)
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®)+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.
Document Type: Research Article
Affiliations: 1: Department of Medical Ultrasound, The Third Affiliated Hospital of Guangzhou Medical College, Guangdong, 510150, China, Email: email@example.com 2: Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical College, Guangdong, China 3: Department of Ultrasonography, Union Hospital, Tongji Medical Collegen, Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
Publication date: January 1, 2009