Combination of adenovirus-mediated thymidine kinase gene therapy with cytotoxic chemotherapy in bladder cancer in vitro.

摘要: We evaluated efficacy, toxicity and potential synergism of adenoviral-mediated thymidine kinase (tk)- ganciclovir (GCV) gene therapy in combination with 4 cytotoxic chemotherapeutic agents (doxorubicin, cisplatin, mitomycin C, methotrexate) 3 human bladder cancer cell lines. Cell lines were exposed to (1) 10 different concentrations adenovirus expressing tk plus GCV; (2) 8 either doxorubicin, methotrexate, C or cisplatin; (3) treatment consisting low-, medium- high-dose tk-GCV a single agent. survival was determined using MTT-based proliferation-assay. For most combinations, adding chemotherapy did not result any therapeutic benefit. In some scenarios, we observed modest improvement combinations standard over monotherapy. Low methotrexate enhanced the antitumor effects low- medium-dose therapy. level negative interference between occurred but overall negligible. general, demonstrate significant benefit vitro. High doses should be used order take advantage occasional instance where Additional studies exploring role enhancing system are required. Investigation other, potentially more synergistic is warranted.