Browse > Article

Chemosensitization of Human Ovarian Carcinoma Cells by a Recombinant Adenoviral Vector Containing L-plastin Promoter Fused to Cytosine Deaminase Transcription Unit  

Chung, In-Jae (College of Pharmacy, Duksung Women's University)
Publication Information
Biomolecules & Therapeutics / v.13, no.3, 2005 , pp. 143-149 More about this Journal
Abstract
We have demonstrated previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase (CD) gene is driven by the tumor-specific L-plastin promoter. The object of this study was to evaluate the efficacy of AdLPCD together with 5-fluorocytosine (5-FC) in suppression of the growth of established human tumor cells of ovary, Consistent with the knowledge that infection of OVCAR-3 cells with AdLPCD resulted in expression of a functional intracellular CD enzyme capable of converting 5-FC to 5-fluorouracil (5-FU) (Chung and Deisseroth, 2004), statistically significant differences in cytotoxicity were observed when AdLPCD infected cells were also exposed to 5-FC for 6 days (p=0.05), 9 days (p<0.0005) and 12 days (p<0.005), compared to 5-FC exposure alone, These results indicate that the CD gene delivered by adenoviral vector could efficiently sensitize OVCAR-3, otherwise non-toxic 5-FC. On the other hand, SKOV-3 cells, an ovarian carcinoma cell line, were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The results of present study suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.
Keywords
L-plastin promoter; tumor-specific promoter; adenoviral vector; gene therapy; ovarian cancer; cytosine deaminase;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Akbulut, H., Zhang, L., Tang, Y., and Deisseroth, A. (2003). Cytotoxic effect of replication-competent adenoviral vectors carrying L-plastin promoter regulated E1A and cytosine deaminase genes in cancers of the breast, ovary and colon. Cancer Gene Ther. 10, 388-395   DOI   ScienceOn
2 Akbulut, H., Tang, Y., Maynard, J., Zhang, L., Pizzomo, G., and Deisseroth, A. (2004). Vector targeting makes 5-fluorouracil chemotherapy less toxic and more effective in animal models of epithelial neoplasms. Clin. Cancer Res. 10, 7738-7746   DOI   ScienceOn
3 Anderson, L., Kilstrup, M., and Neuhard, J. (1989). Pyrimidine, purine and nitrogen conrol of cytosine deaminase synthesis in Escherichia coli K12. Involvement of the glinG and purR genes in the resgulation of codA expression. Arch. Microbial. 152, 115-118   DOI   ScienceOn
4 Armstrong, R. D., Lewis, M., Stem, S. G., and Cadman, E. C. (1986). Acute effect of 5-fluorouracil on cytoplasmic and nuclear dihydrofolate reductase messenger RNA metabolism. J. Biol. Chem. 261, 7366-7371
5 Austin, E. A., and Huber, B. E. (1993). A first step in the development of gene therapy for colorectal carcinoma: cloning, sequencing, and expression of E. coli cytosine deaminse. Mol. Pharmacol. 43, 380-387
6 Bergelson, J. M., Cunningham, J. A., Droguett, G., Kurt-Jones, E. A., Krithivas, A., Hong, J. S., Horwitz, M. S., Crowell, R. L., and Finberg, R. W. (1997). Isolation of a common receptor for cosackie B viruses and adenoviruses 2 and 5. Science. 275, 1320-1323   DOI
7 Garcia-Sanchez, F., Pizzorno, G., Fu, S. Q., Nanakom, T., Krause, D. S., Liang, J., Adams, E., Leffert, J. J., Yin, L. H., Cooperberg, M. R., Hanania, E., Wang, W. .L., Won, J. H., Peng, X. Y., Cote, R., Brown, R., Burtness, B., Giles, R., Crystal, R., and Deisseroth, A. B. (1998). Cytosine deaminase adenoviral vector and 5-fluorocytosine selectively reduce breast cancer cells 1 million-fold when they contaminate hematopoietic cells: a potential purging method for autologous transplantation. Blood 92, 672-682
8 Graham, F. L., and Prevec, L. (1991). Manipulation of adenovirus vectors, Methods in molecular biology, Vol. 7, p109-128, E. J. Murray, The Human Press Inc., Clifton, NJ
9 Hirschowitz, E. A., Ohwada, A, Pascal, W. R., Russi, T. J., and Crystal, R. G. (1995). In vivo adenovirus-mediated gene transfer of the Escherichia coli cytosine deaminase gene to human colon carcinoma-derived tumors induces chemosensitivity to 5-fluorocytosine. Hum. Gene Ther. 6, 1055-1063   DOI   ScienceOn
10 Huber, B. E., Austin, E. A., Good, S. S., Knick, V. C., Tibbels, S., and Richards, C. A., (1993). In vivo antitumor activity of 5-fluorocytosine on human colorectal carcinoma cells genetically codified to express cytosine deaminase. Cancer Res. 3, 4619-4626
11 Kievit, E., Nyati, M. K., Ng, E., Stegman, L. D., Parsels, J., Ross, B. D., Rehemtulla, A., and Lawrence, T. S. (2000). Yeast cytosine deaminase improves radiosensitization and bystander effect by 5-fluorocytosine of human colorectal cancer xenografts. Cancer Res. 60, 6649-6655
12 Kufe, D. W., and Major, P. P. (1981). 5-Fluorouracil incorporation into human breast carcinoma RNA correlates with cytotoxicity. J. Biol. Chem. 256, 9802-9805
13 Leavitt, J. (1994). Discovery and characterization of two novel huamn cancer-related proteins using two-dimensional gel electrophoresis. Electrophoresis 15, 345-357   DOI   ScienceOn
14 Peng, X. Y., Won, J. H., Rutherford, T., Fujii, T., Zelterman, D., Pizzorno, G., Sapi, E., Leavitt, J., Kacinski, B., Crystal, R., Schwartz, P., and Deisseroth, A. (2001). The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines. Cancer Res. 61, 4405-4413
15 Lin, C.-S., Chen, Z. P., Park, T., Ghosh, K., and Leavitt, J. (1993a). Characterization of the human L-plastin gene promoter in normal and neoplastic cells. J. Biol. Chem. 268, 2793-2801
16 Lin, C.-S., Park, T., Chen, Z. P., and Leavitt, J. L. (1993b). Human plastin genes. J. Biol. Chem. 268, 2781-2792
17 Moolten, F. L. (1994). Drug sensitivity (suicide) genes for selective cancer chemotherapy. Cancer Gene Ther. 1, 279-287
18 Pritchard, D. M., Watson, A. J., Potten, C. S., Jackman, A. L., and Hickman, J. A. (1997). Inhibition by uridine but not thymidine fo p53-dependent intestinal apoptosis initiated by 5-fluorouracil: evidence for the involvement of RNA perturbation. Proc. Natl. Acad. Sci. USA 94, 1795-1799
19 Wickham, T. J., Mathias, P., Cheresh, D. A., and Nemerow, G. (1993). Integrins ${\alpha}v{\beta}3$ and ${\alpha}v{\beta}5$ promote adenovirus internalization but not virus attachment. Cell. 73, 309-319   DOI   ScienceOn
20 Wickham, T. J., Filardo, E. J., Cheresh, D. A., and Nemerow, G. R. (1994). Integrin ${\alpha}v{\beta}5$ selectively promotes adenovirus mediated cell membrane permeabilization. J. Cell. Biol. 127, 257-264   DOI   ScienceOn
21 Zhang, L., Akbulut, H., Tang, Y., Peng, X., Pizzorno, G, Sapi, E., Manegold, S., and Deisseroth, A. (2002). Adenoviral vectors with E1A regulated by tumor-specific promoters are selectively cytolytic for breast cancer and melanoma. Mol. Ther. 6, 386-393   DOI   ScienceOn
22 Cannistra, S. A. (1995). Cancer of the ovary. N. Engl. J. Med. 329, 1550-1559   DOI   ScienceOn
23 Chung, I., and Deisseroth, A. B. (2004). Recombinant adenoviral vector containing tumor-specific L-plastin promoter fused to cytosine deaminase gene as a transcription unit: generation and functional test. Arch. Pharm. Res. 27, 633-639   DOI   ScienceOn
24 Higashiyama, M., Kodama, K., Yokouchi, H., Takami, K., Doi, O., Kobayashi, H., Tanisaka, K., and Minamigawa, K. (1998). Immunohistochemical p53 protein status in nonsmall cell lung cancer is a promising indicator in dterrnining in vitro chemosensitivity to some anticancer drugs. J. Surg. Oncol. 68, 19-24   DOI   ScienceOn
25 Goldman, M. J., and Wilson, J. M. (1995). Expression of ${\alpha}V{\beta}3$ and ${\alpha}V{\beta}5$ integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway. J. Virol. 69, 5951-5958
26 Chung, I., Schwartz, P. E., Crystal, R. G., Pizzomo, G., Leavitt, J. L., and Deisseroth, A. B. (1999). Use of L-plastin promoter to develop adenoviral system which confers transgene expression in ovarian cancer cells but not in normal mesothelial cells. Cancer Gene Ther. 6, 99-106   DOI   ScienceOn
27 Glazer, R. I., and Lloyd, L. S. (1982). Association of cell lethality with incorporation of 5-fluorouracil and 5-fluoridine into nuclear RNA in human colon carcinoma cells in culture. Mol. Pharmacol. 21, 468-473
28 Lenz, H. J., Hayashi, K., Salonga, D., Danenberg, K. D., Danenberg, P. V., Metzger, R., Banerjee, D., Bertino, J. R., Groshen, S., Leichman, L. P., and Leichman, C. G. (1998). p53 point mutations and thymidylate synthase messenger RNA levels in disseminated colorectal cancer: an analysis of response and survival. Clin. Cancer Res. 4, 1243-1250