Research Project
Grant-in-Aid for Scientific Research (B)
We examined p53 gene therapy combined with radiation or hyperthermia using several human cancer cell lines transfected with wild-type p53 (wtp53) or mutated p53 gene (mp53). Transfection with wtp53 to p53-null lung cancer cells (H1299) increased the radiosensitivity and enhanced radiation-induced apoptosis. Human anaplastic thyroid carcinoma cells (8305c bearing mp53) transfected with temperature sensitive mp53 showed an enhanced radiation or heat sensitivity and apoptosis under 32℃ culture condition of expression of wtp53 phenotype. Human squamous cell carcinoma (SAS bearing wtp53 phenotype) cells transfected with rsp53 were resistant to X-ray compared with the control cells having normal function of p53 (SAS/neo). SAS/neo tumor-transplanted nude mice showed a delayed rumor growth compared with SAS/mp53 tumor-transplanted nude mice after treatment with X-ray or hyperthermia. From these results, p53 gene therapy combined with radiation and hyperthermia therapies might improve the outcome of cancer therapies.
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