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OALib Journal期刊
ISSN: 2333-9721
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血管内皮生长因子受体启动子驱动重组腺病毒双自杀基因系统选择性杀伤大肠癌细胞
, PP. 524-527
Keywords: 结直肠肿瘤,血管内皮,kdr启动子,自杀基因治疗
Abstract:
目的探讨血管内皮生长因子受体(kdr)启动子驱动重组腺病毒cdglytk融合基因体系对结直肠癌细胞株lovo及人脐血管内皮细胞株ecv30的选择性杀伤作用.方法将质粒padeasy-kdr-cdglytk在293细胞内包装、扩增后,体外感染表达kdr的lovo、ecv30细胞和对照组不表达kdr的ls17t细胞,并给予不同浓度的前药gcv(ganciclovir)和/或5-fc(5-fluorocytosine),观察该体系对细胞株的杀伤效应.结果制备的病毒滴度为2.0×1012pfu/ml.3种细胞的感染率相似,且感染率随腺病毒滴度的递增而增加,当moi为200时,所有细胞株均接近100%感染.以moi为100的重组体分别感染各细胞株,发现其对前药的敏感性不同:表达kdr的lovo和ecv30细胞对前药具有较高的敏感性,且二者敏感性无显著差异(p>0.1);与前二者相比,ls17t细胞对前药不敏感(p<0.001).同时,cdglytk双自杀基因的疗效优于任一单自杀基因(p<0.001).流式细胞术检测表明该体系抑制lovo细胞dna的合成,表现为s期细胞比率增多及g1期细胞减少(p<0.001).结论kdr基因启动子调控的cdglytk融合基因体系可选择性杀伤结直肠癌lovo细胞和血管内皮细胞.
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