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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 investigate the cytotoxicity of adenovirus vector-mediated cytosine deaminase (CD) gene transfection and CD/5 FC on human rectal cancer cells. Methods Adenovirus-mediated transfer of exogenous CD gene to human rectal cancer cell line HR 834 8 was used to detect the transduction efficiency of adenovirus, CD gene expression, colony formation assay, and cell viability assay. Experiments were performed to observe the killing effect of CD/5 FC on cancer cells. Results The recombinant adenovirus-mediated transfection of CD gene was highly expressed in cancer cells. CD/5 FC system significantly inhibited the colony formation and cell growth of transfected HR 834 8 cells containing CD, but had no effect on the transfection of cancer cells without CD gene. In the HR 834 8 mixed system with and without transfection of CD gene, CD/ 5 FC showed significant cytotoxicity against the surrounding non-CD transfected cancer cells in addition to killing the cancer cells transfected with the CD gene. Strong “bystander effect.” The results of subcutaneous xenograft cancer treatment in nude mice showed that the inhibition rate of CD/5 FC on HR 834 8 solid cancer was 71.5%. Conclusion CD / 5 FC has a strong killing effect on adenovirus-mediated CD gene transfected rectal cancer cells and a significant “bystander effect”.