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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adenoviridae, Antimetabolites, Antineoplastic, Antineoplastic Agents, Carcinoma, Hepatocellular, Cell Line, Tumor, Colonic Neoplasms, DNA, Viral, Dose-Response Relationship, Drug, Fluorouracil, Gene Expression Regulation, Neoplastic, Genetic Vectors, Humans, Hydroxyurea, Liver Neoplasms, Microscopy, Confocal, Polymerase Chain Reaction, Time Factors, Transgenes, beta-Galactosidase.
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Do 5-fluorouracil and hydroxyurea enhance adenovirus-mediated transgene expression in colon and hepatocellular carcinoma cells? Context: To investigate the efficient transduction of tumor cells which remains a major limitation of cancer gene therapy. In this study, we tested whether treatment with antimetabolic drugs 5-FU and hydroxyurea (HU) could improve adenovirus-mediated gene expression in tumor cells. We found that 5-FU and HU treatment significantly increased beta-gal activity in adenovirus (Ad.CMVBG)-infected human colon carcinoma (LoVo) and hepatocellular carcinoma (SMMC7721) cells in a dose- and time-dependent manner. These increases were maximized at 5.01+/-0.42-fold and 3.32+/-0.32-fold for 5-FU (50 microM), and at 6.60+/-0.50-fold and 4.82+/-0.43-fold for HU (5 mM) treatment, respectively, after 48 h infection. Transient increases in viral uptake, determined by real-time PCR for viral DNA content and by confocal microscopy for viral particles, were observed in 5-FU or HU-treated cells that partially contribute to the overall increases of beta-gal expression. Moreover, mRNA levels for the beta-gal gene in infected cells were significantly increased in both LoVo and SMMC7721 cells by 5-FU and HU treatment in contrast to the inhibition of viral DNA replication and the unchanged mRNA levels for alpha-actin gene. The induction appeared to be the result of enhanced transcription since beta-gal mRNA half-life was not affected by drug treatment. However, similar induction was not detected in CMV-beta-gal-expressing stable cells, suggesting that an adenovirus-associated mechanism might be involved in this induction.
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Our findings suggest that it may be possible to improve tumor cell transduction by adenovirus using chemotherapy. Final Decision: yes