Liu T J, Zhang W W, Taylor D L, Roth J A, Goepfert H, Clayman G L
Department of Head and Neck Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1994 Jul 15;54(14):3662-7.
Mutations of the p53 gene constitute one of the most frequent genetic alterations in squamous cell carcinoma of the head and neck (SCCHN). In this study, we introduced wild-type p53 into two separate SCCHN cell lines via a recombinant adenoviral vector, Ad5CMV-p53. Northern blotting showed that following infection by the wild-type p53 adenovirus (Ad5CMV-p53), cells produced up to 10-fold higher levels of exogenous p53 mRNA than cells treated with vector only (without p53). Western blotting showed that the increased levels of p53 protein produced in the Ad5CMV-p53-infected cells were a reflection of p53 mRNA expression. In vitro growth assays revealed growth arrest following Ad5CMV-p53 infection as well as cell morphological changes consistent with apoptosis. In vivo studies in nude mice with established s.c. squamous carcinoma nodules showed that tumor volumes were significantly reduced in mice that received peritumoral infiltration of Ad5CMV-p53. These data suggest that Ad5CMV-p53 may be further developed as a potential novel therapeutic agent for SCCHN since introduction of wild-type p53 into SCCHN cell lines attenuates their replication and tumor growth.
p53基因的突变是头颈部鳞状细胞癌（SCCHN）中最常见的基因改变之一。在本研究中，我们通过重组腺病毒载体Ad5CMV-p53将野生型p53导入两个不同的SCCHN细胞系。Northern印迹分析表明，野生型p53腺病毒（Ad5CMV-p53）感染后，细胞产生的外源性p53 mRNA水平比仅用载体处理（无p53）的细胞高10倍。Western印迹分析表明，Ad5CMV-p53感染细胞中p53蛋白水平的升高反映了p53 mRNA的表达。体外生长试验显示，Ad5CMV-p53感染后细胞生长停滞，且细胞形态发生与凋亡一致的变化。在已建立皮下鳞状癌结节的裸鼠体内研究表明，接受Ad5CMV-p53瘤周浸润的小鼠肿瘤体积显著减小。这些数据表明，由于将野生型p53导入SCCHN细胞系可减弱其复制和肿瘤生长，Ad5CMV-p53可能作为一种潜在的新型SCCHN治疗药物而得到进一步开发。
