Enhancement of radiotherapy and hyperthermia by transfection with cancer suppressor gene

我们使用几种转染了野生型p53 （wtp53）或突变p53基因（mp53）的人类癌细胞系研究了p53基因治疗联合放疗或热疗。转染wtp53到p53缺失的肺癌细胞（H1299）后，放射敏感性增加，辐射诱导的细胞凋亡增强。转染温度敏感型mp53的人甲状腺间变性癌细胞（8305c携带mp53）在32℃培养条件下表达wtp53表型，显示出辐射或热敏性增强和凋亡。与具有正常p53功能的对照细胞（SAS/neo）相比，转染rsp53的人鳞状细胞癌（SAS携带wtp53表型）细胞对x射线具有抗性。与SAS/mp53裸鼠相比，经x线或热疗治疗后，SAS/neo裸鼠的肿瘤生长延迟。从这些结果来看，p53基因治疗联合放疗和热疗可能会改善癌症治疗的结果。

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.