腺病毒介导胞嘧啶脱氨酶基因对直肠癌细胞的杀伤作用

Antitumor effect of adenovirus mediated cytosine deaminase gene on rectal cancer cells

目的探讨腺病毒载体介导的胞嘧啶脱氨酶 (CD)基因转染和CD/ 5 FC对直肠癌细胞的杀伤作用。方法用重组腺病毒介导外源CD基因转移到人直肠癌细胞株HR 834 8,通过检测腺病毒的转导效率、CD基因表达 ,以及集落形成实验、细胞存活率测定 ,裸鼠移植癌治疗实验 ,观察分析CD/ 5 FC对癌细胞的杀伤作用。结果重组腺病毒介导CD基因转染 ,在癌细胞中得到高效表达。CD/ 5 FC系统对转染含CD重组腺病毒HR 834 8细胞的集落形成、细胞生长均有明显的抑制作用 ,而对无CD基因转染癌细胞无影响。在转染和未转染CD基因的HR 834 8混合体系中 ,CD/ 5 FC除了杀伤转染CD基因的癌细胞外 ,对周围的无CD转染癌细胞也有明显的杀伤作用 ,表现出很强的“旁观者效应”。裸鼠皮下移植癌治疗实验结果表明 ,CD/ 5 FC对HR 834 8实体癌生长抑制率为 71 5 %。结论CD/ 5 FC对腺病毒介导CD基因转染的直肠癌细胞有很强的杀伤作用和显著的“旁观者效应”。

Objective To evaluate antitumor effect of adenovirus-mediated cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) on rectal cancer cells.MethodsCD gene was transinfected into HR-8348 rectal cacer cell lines with recombinant adenovirus mediation. The transinfection rate and expression of CD gene were detected. Plating efficiency and MTT method were used to examine inhibition of HR-8348 cell growth, and antitumor effect of CD/5-FC were evaluated on HR-8348 experimental tumor in nude mice.ResultsHigh transinfection effeciency and expression of CD gene were achieved in HR-8348 with adenovirus mediation. CD/5-FC system showed a remarkble effect of inhibition on plating efficiency and growth of the tumor cells transinfected with CD gene, but no act on tumor cells without CD gene transinfection. In a mixture of HR-8348 tumor cells with and without CD gene transinfection, CD/5-FC killed both types of tumor cells and revealed a powerful 'by-stander effect'. With nude mice experiment, 71.5% of inhibition of solid tumoral xenografts of HR-8348 cells was found.ConclutionCD/5-FC has significant antitumor effect on rectal cancer cells with adenovirus-mediated CD gene transinfection and has also 'by-stander effect' on tumor cells.