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- Title
Antitumor effect of mSurvivinThr34 → Ala in murine colon carcinoma when administered intravenously.
- Authors
Li, Hong-xia; Zhao, Xin-yu; Wang, Lian; Wang, Yong-sheng; Kan, Bin; Xu, Jian-rong; Li, Jiong; Wen, Yan-Jun; Peng, Xing-chen; Chen, Xiang; Yan, Fei; Ye, Bin; Du, Xiao-bo; Zhao, Ju-mei; Yi, Tao; Chen, Xian-cheng; Du, Xiao-xia; Wei, Yu-quan; Zhao, Xia
- Abstract
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 Cr 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.
- Subjects
COLON cancer; ANTINEOPLASTIC agents; LABORATORY mice; INTRAVENOUS therapy; APOPTOSIS; T cells; NEOVASCULARIZATION; CELL-mediated cytotoxicity; LIPOSOMES
- Publication
Medical Oncology, 2010, Vol 27, Issue 4, p1156
- ISSN
1357-0560
- Publication type
Article
- DOI
10.1007/s12032-009-9353-2