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目的：探讨ＣＤ基因对大肠癌组织靶向治疗的作用。方法：构建以ＣＥＡ基因顺式转录调控序列（ＴＲＳ）驱动ＣＤ基因的组织特异性重组逆转录病毒载体Ｇ１ＣＥＡＣＤＮａ，脂质体包裹法将重组组织特异性载体及ｐＣＤ２ 在逆转录病毒包装细胞ＰＡ３１７细胞中进行包装，收获病毒上清后分别转染入高分泌ＣＥＡ的大肠癌细胞ＬｏＶｏ 中，经Ｇ４１８ 筛选阳性克隆扩增后进行体外前药敏感实验及观察旁观者效应，然后再将转基因ＬｏＶｏ 细胞接种到裸鼠皮下成瘤，进行体内抑瘤实验。结果：与对照组比较，转ＣＤ基因肿瘤细胞对５－ＦＣ的敏感性显著增高（Ｐ＜ ０．０１），其ＩＣ５０ 分别为０．１ ｍ ｍ ｏｌ／Ｌ和０．５ ｍ ｍ ｏｌ／Ｌ，同时发现转ＣＤ基因细胞在５－ＦＣ作用下可产生强效的旁观者杀伤效应；ＬｏＶｏ 细胞接种到裸鼠皮下，２ 周均已成瘤，此时将前药５－ＦＣ腹腔注射，治疗６０ ｄ 后，肿瘤生长较对照组明显缩小（Ｐ＜ ０．０５， ｎ＝ １０）。结论：ＣＥＡＴＲＳ可调控自杀基因在ＣＥＡ阳性分泌大肠癌细胞中特异性表达，以达到靶向杀伤肿瘤的目的。
Objective: To investigate the role of CD gene in targeted therapy of colorectal cancer. METHODS: A tissue-specific recombinant retroviral vector G1CEACDNa was constructed by using the CEA gene cis-transcriptional regulatory sequence (TRS) to drive the CD gene. The recombinant tissue-specific vector and pCD2 were packaged in retrovirus packaging cells PA317 cells by liposome entrapment. After packaging, virus supernatants were harvested and transfected into high-secreted CEA colorectal cancer cells LoVo respectively. G418 screening positive clones were used for in vitro prodrug sensitization experiments to observe bystander effects, and then transgenic LoVo cells were inoculated. Nude mice were subcutaneously tumor-bearing and tumor-bearing experiments were performed in vivo. RESULTS: Compared with the control group, the sensitivity of transfected CD gene tumor cells to 5-FC was significantly higher (P<0.01), and the IC50 was 0.1 m m ol/L and 0.5 m m ol/L, respectively. At the same time, it was found that transduced CD gene cells could produce a strong bystander killing effect under 5-FC; LoVo cells were inoculated subcutaneously into nude mice and became tumorigenic at 2 weeks. At this time, the prodrug 5-FC was intraperitoneally injected. After 60 days, the tumor growth was significantly smaller than that of the control group (P < 0.05, n = 10). Conclusion: CEATRS can regulate the specific expression of suicide gene in CEA positively-secreting colorectal carcinoma cells, so as to achieve the purpose of killing the tumor.