title: Study of the UTMD-based delivery system to induce cervical cancer cell apoptosis and inhibit proliferation with shRNA targeting Survivin.
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.
authors: Department of Medical Ultrasound, Key Laboratory for Major Obstetric Diseases of Guangdong Province, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China. winchen@vip.126.com.
authors: Zhi-Yi
authors: ZY
authors: Chen
authors: Kun
authors: K
authors: Liang
authors: Yan
authors: Y
authors: Lin
authors: Feng
authors: F
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001808:Blood Vessels / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D045423:Microbubbles; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D011897:Random Allocation; D000077022:Survivin; D047368:Tumor Burden / Q000235:genetics; D014465:Ultrasonics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D000077022:Survivin; D053148:Caspase 3