p53 gene therapy for esophageal cancer

背景：尽管围手术期辅助治疗有所改进，但许多晚期食道癌患者的存活率仍然很低。P53基因功能改变是食道癌发生发展的重要因素。我们检测了腺病毒介导的野生型p53基因转移在体内外对有和没有p53基因突变的人食管鳞癌细胞增殖的影响，以检验其临床应用的能力。方法：选择7株p53基因突变的人食道癌细胞株(EGGI-10、T.Tn、TE-1、TE-10、TE-11、TE-13)和1株未发生p53基因突变的细胞株(TE-2)。TE-10、TE-11、TE-13、EGGI-10有明显的p16基因改变。通过感染重组P53腺病毒载体或LacZ载体，在体外检测这些细胞系的转导效率、P53表达和生长抑制。在荷T.Tn肿瘤的裸鼠体内评价其对肿瘤生长的抑制作用。结果：100个MOI的转染率为60%。体外生长实验显示，30个或更多MOI的P53腺病毒载体对裸鼠的生长有明显的抑制作用，裸鼠体内实验表明，瘤内注射P53腺病毒载体的小鼠肿瘤体积减小。结论：P53腺病毒载体有可能成为治疗局部晚期食道癌的潜在药物。

Background ; Despite improvements in perioperative adjuvant therapy, survival ratio is still very low among many patients with advanced esophageal cancer. Alteration of the p53 gene function is a major factor in the development of esophageal cancer. We examined the efficacy of an adenovirus- mediated wild-type p53 gene transfer on the proliferation of human esophageal squamous cell carcinoma cells with and without p53 gene mutation in in vitro as well as in vivo to test the ability of clinical application. Methods ; Seven human esophageal cancer cell lines (EGGI-10, T.Tn, TE-1, TE-10, TE-1 1, TE-13) with p53 alteration and one cell lines (TE-2) without p53 alteration were used. p16 genetic alteration was evident in TE-10, TE-1 1, TE-13, EGGI-10. The transduction efficiency, p53 expression, and growth suppression were assessed in in vitro in these cell lines by infecting the recombinant p53 adenoviral vector or LacZ vector. The tumor growth suppression in vivo was assessed in nude mice bearing T.Tn tumors. Results ; The trasnduciton efficiency was 60% with 100 MOI infection. In vitro growth assays revealed significant growth suppression following 30 or more MOI of p53 adenoviral vector, In vivo studies in nude mice showed that tumor volume were reduced in mice that received intratumoral injection of p53 adenoviral vector. Conclusion ; These data suggest that p53 adenoviral vector may be a potential therapeutic agent for locally advanced esophageal cancer.