PUBLICATION
A novel strategy for tumor therapy combining cell apoptosis and active immunity induced by caspy2, a zebrafish caspase
- Authors
- Liu, L., Deng, H., Wang, Y., Chen, P., Yang, Y., Yang, H., Chen, X., Chen, L., Zhu, W., Liang, S., Yang, J., Qian, Z., Li, J., Wen, Y., Kan, B., Mao, Y., Zhao, X., and Wei, Y.
- ID
- ZDB-PUB-090227-1
- Date
- 2009
- Source
- Journal of Cellular and Molecular Medicine 13(8b): 2271-2281 (Journal)
- Registered Authors
- Zhao, Xia
- Keywords
- apoptosis, immune response, plasmid DNA, cationic liposome, dual effect
- MeSH Terms
-
- Animals
- Apoptosis/physiology*
- Base Sequence
- Caspases/physiology*
- DNA Primers
- Mice
- Zebrafish
- Zebrafish Proteins/physiology*
- PubMed
- 19220579 Full text @ J. Cell. Mol. Med.
Citation
Liu, L., Deng, H., Wang, Y., Chen, P., Yang, Y., Yang, H., Chen, X., Chen, L., Zhu, W., Liang, S., Yang, J., Qian, Z., Li, J., Wen, Y., Kan, B., Mao, Y., Zhao, X., and Wei, Y. (2009) A novel strategy for tumor therapy combining cell apoptosis and active immunity induced by caspy2, a zebrafish caspase. Journal of Cellular and Molecular Medicine. 13(8b):2271-2281.
Abstract
Caspy2, a zebrafish protease, is an active caspase for inducing apoptosis in mammalian cells. To investigate whether caspy2-mediated apoptosis could be used in cancer therapy, its cDNA was amplified and cloned into eukaryotic expression vector pcDNA3.1 (+). The recombinant plasmid was mixed with cationic liposome and introduced into various tumor cell lines in vitro. Our data showed that caspy2 induced remarkable apoptosis of cancer cells in vitro. Treatment of mice bearing CT26 colon carcinoma or MethA fibrosarcoma with intratumoral injection of liposome-caspy2 plasmid complex resulted in substantial kill of neoplastic cells and long-term survivors. Apoptotic cells were widely distributed in caspy2 treated tumor tissue. Infiltration of CD8(+) T lymphocyte was also observed apparently in the tumor tissue after the treatment with caspy2. Tumor specific MHC class I-dependent CD8(+) cytotoxic T lymphocyte (CTL) activity was found by means of (51)Cr release assay. In MethA model, the mice acquired a longtime protective immunity against the parental tumor cell re-challenge. These results indicated that caspy2 can act as both apoptosis inducer and immune response initiator, which may account for its extraordinary antitumor effect. Furthermore, in vivo depletion of CD8(+) T lymphocytes could completely abrogate the antitumor immune activity, whereas the depletion of CD4(+) cells showed partial abrogation. In this study, we developed a novel anticancer strategy that combines both induction of apoptosis and immune response in mice bearing tumors with a single caspy2 gene. This approach may provide an important way for treatment of cancer.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping