Abstract
Apoptosis induction by short hairpin RNA (shRNA) expression vectors could be an efficient and promising strategy for cancer gene therapy. Ultrasound-targeted microbubble destruction (UTMD) is an appealing technique. In this study, we investigated the apoptosis induction and suppression of cell proliferation in vivo transfected by the UTMD-based shRNA delivery system. Nude mice with transplanted tumors of cervical cancer were randomly arranged into three groups: control group, plasmid injection and ultrasound (P + US), P + UTMD group. Expressions of Survivin and proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, Caspase-3, Ki-67, nucleostemin (NS) were investigated by immunohistochemistry. Furthermore, microvessel density (MVD) was detected by CD34 protein expressions and apoptotic index (AI) was measured by TUNEL. As compared with those in the control and P + US groups, protein expressions of PCNA, Ki-67, Bcl-2, Survivin and NS in P + UTMD groups were down-regulated markedly, while those of Bax, Caspase-3 were up-regulated significantly (p < 0.05). MVD decreased significantly, whereas AI increased remarkably (p < 0.05). We suggested that UTMD-based shRNA delivery system could induce apoptosis and inhibit proliferation significantly, without causing any apparently adverse effect, representing a new, promising technology that would be used in the future gene therapy and research.
Highlights
In recent years, gene silencing mediated by RNA interference (RNAi) technology shows therapeutic potential on solid cancer, and an in-human Phase I clinical trial that used a targeted nanoparticle-delivery system has been conducted [1]
Among non-viral gene transfer methods, it has been shown that ultrasound targeted microbubbles destruction (UTMD) increases cell membrane permeabilization and induces sonoporation, which has been explored to provide a safe and potentially effective approach for gene delivery
We have described a study of UTMD combined with short hairpin RNA (shRNA) technique
Summary
Gene silencing mediated by RNA interference (RNAi) technology shows therapeutic potential on solid cancer, and an in-human Phase I clinical trial that used a targeted nanoparticle-delivery system has been conducted [1]. Lots of gene delivery systems such as cationic polymers or liposome exist, which are effective in transfecting cells in vitro. They cannot be used in vivo due to low target specificity. Among non-viral gene transfer methods, it has been shown that ultrasound targeted microbubbles destruction (UTMD) increases cell membrane permeabilization and induces sonoporation, which has been explored to provide a safe and potentially effective approach for gene delivery
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