p53 gene therapy for esophageal cancer

背景;尽管围手术期辅助治疗有所改善，但许多晚期食管癌患者的生存率仍然很低。p53基因功能的改变是食管癌发生发展的重要因素。我们在体外和体内研究了腺病毒介导的野生型p53基因转染对携带和不携带p53基因突变的人食管鳞状细胞癌细胞增殖的影响，以检验其临床应用能力。方法;使用7株p53改变的人食管癌细胞系（EGGI-10、t.n、TE-1、TE-10、TE-1 1、TE-13）和1株p53未改变的食管癌细胞系（TE-2）。TE-10、TE-1 1、TE-13、EGGI-10中p16基因明显改变。通过感染重组p53腺病毒载体或LacZ载体，在体外评估这些细胞系的转导效率、p53的表达和生长抑制。对携带T.Tn肿瘤的裸鼠进行体内肿瘤生长抑制实验。结果;100 MOI感染时，转导率为60%。体外生长实验显示，p53腺病毒载体MOI≥30次后，细胞生长受到明显抑制。裸鼠体内实验表明，瘤内注射p53腺病毒载体后，小鼠肿瘤体积减小。结论;这些数据提示p53腺病毒载体可能是局部晚期食管癌的潜在治疗剂。

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.