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目的研究ｃｄ基因对大肠肿瘤的特异杀伤作用，探索自杀基因靶向治疗大肠癌的有效途径．方法逆转录病毒感染法将Ｇ１ｃｅａｃｄＮａ及ｐｃｄ２分别转导入高分泌ＣＥＡ的大肠癌细胞Ｌｏｖｏ中，再分别接种到裸鼠皮下．成瘤后腹腔给予５ＦＣ（５００ｍｇ／ｋｇ）治疗，观察肿瘤重量的变化及病理学特点．结果含Ｇ１ｃｅａｃｄＮａ及ｐｃｄ２逆转录病毒载体的病毒滴度分别为：１３×１０７及２１×１０８ＣＦＵ／Ｌ．所有转基因成功并接种动物均成瘤．腹腔给予５ＦＣ治疗后发现，转由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的肿瘤对５ＦＣ的敏感性明显高于转非ｃｅａ调控ｃｄ基因的肿瘤，治疗结束后肿瘤重量分别为３１ｍｇ±８ｍｇ及１１３ｍｇ±２３ｍｇ（Ｐ＜００１）．结论本实验提示ｃｅａ转录调控序列可控制ｃｄ基因在ＣＥＡ阳性的大肠癌组织中高效表达，进而在前药５ＦＣ的作用下发挥选择性杀伤肿瘤的作用
Objective To study the specific killing effect of cd gene on colorectal tumors and explore the effective way of targeting suicide gene therapy for colorectal cancer. Methods Retrovirus infection method was used to transfer G1ceacdNa and pcd2 into Lovo, a colorectal cancer cell with high secretion of CEA, and then inoculated subcutaneously into nude mice. The tumors were given intraperitoneally with 5-FC (500 mg/kg) to observe the changes in tumor weight and pathological features. Results The titer of the retrovirus vector containing G1ceacdNa and pcd2 was: 13×107 and 21×108CFU/L, respectively. All transgenic animals were successfully vaccinated and became tumor-bearing animals. After intraperitoneal administration of 5-FC, it was found that the sensitivity of tissue-specific recombinant retroviral vector G1ceacdNa transferred to the cd gene driven by the CEA gene cis-transcriptional regulatory sequence (TRS) to 5-FC was significantly higher than that to non-cea control. For cd gene tumors, tumor weights after treatment were 31 mg±8 mg and 113 mg±23 mg, respectively (P<001). Conclusion This experiment suggests that ceta transcriptional control sequences can control the high expression of cd gene in CEA-positive colorectal cancer tissues, and then play a role in selectively killing tumors under the action of prodrug 5-FC.