摘要
本实验将ＨＳＶ－ｔｋ基因构建在逆转录病毒载体ＰＬＸＳＮｎｅｏ上，经ＰＡ３１７包装后，筛选出５ｘ１０￣５ｐｆｕ／ｍｌ的ＴＫ包装细胞。用该细胞培养上清感染体外培养细胞，并用Ｇａｎｃｉｃｌｏｖｉｒ－ＧＣＶ处理，可以对增殖的细胞产生细胞毒害作用。细胞增殖速度越快，细胞毒害作用越强。在体内实验中，将ＴＫ细胞直接注射到移植瘤中或与瘤组织悬液混合接种同种小鼠。再用ＧＣＶ治疗，对肿瘤有较强的生长抑制作用。
Although chemotherapy plays a main role in treatment for cancer, gene therapy is thought to be a promising approach of treatment for the future. Thymidine-Kinase gene was delivered into proliferating cells by a retroviral mediated gene transfer system in the culture cells. Later treatment with GCV showed definite cytotoxic effect on the HSV-tk modified cells and the effect correlated with the growth rate of cells. The rapid proliferating tumor cells, HR8348, were inhibited more efficiently than slow proliferating cells. In experiment in vivo , the introduced TK producer cells released virus particles continuously into their neighbor and, as compared with the control, GCV treatment exerted remarkable inhibitory effect on the growth of tumor. The inhibition also correlated with the number of injected TK producer cells. With administration of 0.2 ml of #795 tumor cell suspension(100 ng/ml), coinjection of 2 ×106 TK producer cells achieved 37% inhibition while that of 1 ×107 TK producer cells achieved 66% inhibition,though complete regression could not be achieved under such circumstances.Our result suggests that TK gene transfer followed by GCV treatment merits further evaluation as an effective antineoplastic approach.
