PMID- 19949901 OWN - NLM STAT- MEDLINE DCOM- 20110408 LR - 20211020 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 27 IP - 4 DP - 2010 Dec TI - Antitumor effect of mSurvivinThr34-->Ala in murine colon carcinoma when administered intravenously. PG - 1156-63 LID - 10.1007/s12032-009-9353-2 [doi] AB - Colorectal cancer is one of the most common cancers. Survivin is strongly immunogenic in a fraction of colorectal cancer patients. The present study was designed to determine whether full-length mouse Survivin dominant-negative mutant SurvivinT34A has the antitumor activity in a murine colon carcinoma model. The complex of cationic liposome (DOTAP/Chol) to plasmid pORF9-mSurvivin T34A was administered intravenously in a mouse subcutaneous (S. C.) CT 26 tumor model. Apoptotic cells and anti-angiogenesis were evaluated by fluorescent in situ TUNEL assay and by immunohistochemistry with an antibody reactive to CD31, respectively. A 4 h 51Cr release assay was performed to determine Survivin-specific cytotoxicity. The adoptive transfer of CD8+ or CD4+ T-lymphocytes assay was to further explore the roles of immune cell subsets. We demonstrated the complex of cationic liposome (DOTAP/Chol) to plasmid pORF9--mSurvivin T34A when administered intravenously induced an efficient antitumor activity in a S. C. CT26 tumor model in mice. The main mechanism is involved in three aspects: triggering the apoptosis of tumor cells, inhibiting angiogenesis, and inducing Survivin-specific immune response. Our observations may have potential implications for the further exploration of the treatment of human colorectal cancer by intravenous delivery of dominant-negative mutant Survivin T34A. FAU - Li, Hong-xia AU - Li HX AD - Department of Gynecology and Obstetrics, Second West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. FAU - Zhao, Xin-yu AU - Zhao XY FAU - Wang, Lian AU - Wang L FAU - Wang, Yong-sheng AU - Wang YS FAU - Kan, Bin AU - Kan B FAU - Xu, Jian-rong AU - Xu JR FAU - Li, Jiong AU - Li J FAU - Wen, Yan-Jun AU - Wen YJ FAU - Peng, Xing-chen AU - Peng XC FAU - Chen, Xiang AU - Chen X FAU - Yan, Fei AU - Yan F FAU - Ye, Bin AU - Ye B FAU - Du, Xiao-bo AU - Du XB FAU - Zhao, Ju-mei AU - Zhao JM FAU - Yi, Tao AU - Yi T FAU - Chen, Xian-cheng AU - Chen XC FAU - Du, Xiao-xia AU - Du XX FAU - Wei, Yu-quan AU - Wei YQ FAU - Zhao, Xia AU - Zhao X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091201 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (Birc5 protein, mouse) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (Liposomes) RN - 0 (Repressor Proteins) RN - 0 (Survivin) RN - 2ZD004190S (Threonine) RN - OF5P57N2ZX (Alanine) SB - IM MH - Adoptive Transfer MH - Alanine/genetics MH - Animals MH - Apoptosis MH - Blotting, Western MH - CD4-Positive T-Lymphocytes/immunology/metabolism MH - CD8-Positive T-Lymphocytes/immunology/metabolism MH - Cell Adhesion MH - Cell Movement MH - Cell Proliferation MH - Colonic Neoplasms/*genetics/immunology/*therapy MH - Female MH - *Genetic Therapy MH - Humans MH - Immunoenzyme Techniques MH - Inhibitor of Apoptosis Proteins/genetics/immunology/*metabolism MH - Injections, Intravenous MH - Liposomes MH - Mice MH - Mice, Inbred BALB C MH - Neovascularization, Pathologic/*prevention & control MH - Repressor Proteins/genetics/immunology/*metabolism MH - Survivin MH - Threonine/genetics EDAT- 2009/12/02 06:00 MHDA- 2011/04/09 06:00 CRDT- 2009/12/02 06:00 PHST- 2009/07/03 00:00 [received] PHST- 2009/10/27 00:00 [accepted] PHST- 2009/12/02 06:00 [entrez] PHST- 2009/12/02 06:00 [pubmed] PHST- 2011/04/09 06:00 [medline] AID - 10.1007/s12032-009-9353-2 [doi] PST - ppublish SO - Med Oncol. 2010 Dec;27(4):1156-63. doi: 10.1007/s12032-009-9353-2. Epub 2009 Dec 1.