Pirollo K F, Hao Z, Rait A, Jang Y J, Fee W E, Ryan P, Chiang Y, Chang E H
Department of Surgery, Stanford University, California 94305-5328, USA.
Oncogene. 1997 Apr 10;14(14):1735-46. doi: 10.1038/sj.onc.1201116.
Radiation resistant squamous cell carcinoma of the head and neck cell line JSQ-3 carries a mutant form of tumor suppressor gene p53. Treatment of these cells with an adenoviral vector containing wild-type p53 (Av1p53) was able to inhibit their growth in vitro and in vivo while having no effect on normal cells. More significantly, introduction of wtp53 also reduced the radiation-resistance level of this cell line in vitro, in a viral dose-dependent manner. Furthermore, this radiosensitization also carried over to the in vivo situation where the response of JSQ-3 cell-induced mouse xenografts to radiotherapy was markedly enhanced after treatment with Av1p53. Complete, long-term regression of the tumors for up to 162 days was observed when a single dose of Av1p53 was administered in combination with ionizing radiation, demonstrating the effectiveness of this combination of gene therapy and conventional radiotherapy. This sensitization of tumors to radiation therapy by replacement of wtp53 could significantly decrease the rate of recurrence after radiation treatment. Since radiation is one of the most prevalent forms of adjunctive therapy for a variety of cancers, these results have great relevance in moving toward an improved cancer therapy.
头颈部鳞状细胞癌抗辐射细胞系JSQ - 3携带一种肿瘤抑制基因p53的突变形式。用含有野生型p53的腺病毒载体（Av1p53）处理这些细胞，能够在体外和体内抑制其生长，而对正常细胞没有影响。更显著的是，引入野生型p53还能在体外以病毒剂量依赖的方式降低该细胞系的抗辐射水平。此外，这种放射增敏作用在体内也有体现，在用Av1p53处理后，JSQ - 3细胞诱导的小鼠异种移植瘤对放疗的反应明显增强。当单剂量的Av1p53与电离辐射联合使用时，观察到肿瘤完全、长期消退长达162天，证明了这种基因治疗与传统放疗联合的有效性。通过替换野生型p53使肿瘤对放射治疗敏感，可显著降低放疗后的复发率。由于放射是多种癌症最常用的辅助治疗形式之一，这些结果对于改进癌症治疗具有重要意义。
