应用带HSV－TK基因的重组腺病毒的肺癌基因治疗的研究

带有单纯疱疹病毒脱氧胸苷激酶基因（ＨＳＶ－ｔｋ）的腺病毒结合ｇａｎｃｉｃｌｏｖｉｒ（ＧＣＶ）对分裂细胞有很强的杀伤作用。本文报道在感染复数（Ｍ．Ｏ．Ｉ,ＭｕｌｔｉＰｌｉｃｉｔｙｏｆＩｎｆｅｃｔｉｏｎ）达到１０００时对人体肺腺癌细胞Ａ５４９的杀伤几乎达到回１００％。四种人体肺癌细胞株（Ａ５４９,ＬＡＸ,ＳＰＣ,ＳＫＹ）对带ＨＳＶ－ｔｋ的腺病毒（ＡＤＶ／ＲＳＶ－ｔＫ）的杀伤作用表现不同的敏感性。另外,Ａｃｙｃｌｏｖｉｒ（ＡＣＶ）和ＧＣＶ对感染了重组腺病毒ＡＤＶ／ＲＳＶ－ｔＫ的细胞都有一定杀伤作用,但杀伤效果有很大差别;就Ａ５４９而言,ＧＣＶ的杀伤作用比ＡＣＶ高７—８倍。此外ＡＤＶ／ＲＳＶ－ｔｋ结合ＧＣＶ杀伤肿瘤细胞时有“旁观者效应”,即感染了ＡＤＶ／ＲＳＶ－ｔｋ的细胞与未感染细胞混合后,后者也明显地遭到杀伤。

Research on Human Lung Cancer Gene Therapy by RecombinantAdenovirus with HSV-tk

The killer effect of adenovirus-mediated HSV-tk gene and ganciclovir (GCV) system on human lungadenoma cells is reported in this peper. Recombinant adenovirus with M. O. I(Multiplicity of Infection) of1000 resulted in almost 100% A549 cells (human lung edenoma cell) death. By comparing the killer effecton different human lung cancer cells (A549, LAX, SPC and SKY), it is found that different transducedcell lines have different susceptibilities. The transduced cells are susceptible to both GCV and ACV but indifferent extents. The killer effect of GCV on A549 cells is 7 to 8-fold stronger than that of ACV. There isalso a "bystander effect" when ADV/RSV-tk and GCV system take effect. It means that the untransducedcells are killed when mixed with transduced cells.