腺病毒介导的p53基因对喉癌细胞生长的抑制作用

目的探索ｐ５３基因在喉癌基因治疗方面的可行性。方法以人喉癌细胞系Ｈｅｐ－２为实验对象,将载有人野生型ｐ５３ｃＤＮＡ并含巨细胞病毒（ＣＭＶ）启动子的重组腺病毒（Ａｄ５ＣＭＶ－ｐ５３）感染Ｈｅｐ－２细胞及肿瘤组织,体内外实验观察Ａｄ５ＣＭＶ－ｐ５３对Ｈｅｐ－２细胞生长的影响。结果当Ａｄ５ＣＭＶ－ｐ５３在１００ＭＯＩ效靶比时,全部Ｈｅｐ－２细胞得到转染。感染２天后ｐ５３蛋白表达达到高峰,Ｈｅｐ－２生长受到明显的抑制。Ａｄ５ＣＭＶ－ｐ５３感染Ｈｅｐ－２细胞在裸鼠中失去致瘤性。瘤内注射Ａｄ５ＣＭＶ－ｐ５３后,荷瘤裸鼠的肿瘤体积明显减小。结论Ａｄ５ＣＭＶ－ｐ５３转导野生型ｐ５３基因可能是一种有效的喉癌基因治疗途径。

Adenovirus-mediated p53 gene therapy of human laryngeal cancer

OBJECTIVE: To explore the potential use of p53 in gene therapy for laryngeal cancer. METHODS: A human laryngeal cancer cell line Hep-2 was used. Recombinant cytomegalovirus-promoted adeno-viruses containing human wild-type p53 cDNA was transiently introduced into Hep-2 cells in vitro and injected into tumor nodules in vivo. The growth of Hep-2 cells in vitro and established s.c. squamous carcinoma nodules in nude mice was examined. RESULTS: The transduction efficiency of Hep-2 cell line was 100% at > or = 100 MOI. The p53 protein expression peaked on day 2 after infection and lasted far 5 days. Cell growth was greatly suppressed. In vivo studies, Ad5CMV-p53 transfestion in vitro inhibited tumorigenicity of Hep-2 cells in nude mice. Intra-tumoral injection of Ad5CMV-p53 significantly inhibited established s.c. implanted xenograft. CONCLUSION: Transfection of wild-type p53 gene via Ad5CMV-p53 is a potential approach to the therapy of laryngeal cancer.