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目的：探讨单纯疱疹病毒胸苷激酶基因（ＨＳＶ－ｔｋ）、Ｂ细胞活化抗原（Ｂ７）联合基因治疗乳腺癌的协同性。方法： 将ＳＨＺ－８８ 乳腺癌细胞在ＳＤ乳鼠上致瘤后，随机分为对照组、ｔｋ 组、Ｂ７ 组及ｔｋ＋ Ｂ７组，每组１０只。３ 周后瘤体内分别注射空载体０．２ ｍ ｌ或转染有ＧｃＴＫｐＳＮ、ｐＢ７ＳＮ和ＧｃＴＫｐＢ７ＳＮ 基因的ＳＨＺ－８８细胞约５×１０６ 个，并按５０ ｍ ｇ·ｋｇ－ １ ·ｄ－ １腹腔内注射羟甲基无环鸟苷（ＧＣＶ）治疗１５ ｄ，标本以透射电镜观察。结果： ｔｋ 组观察到大量乳腺癌细胞凋亡，Ｂ７ 组肿瘤细胞周围有淋巴细胞聚集，混合组不仅观察到肿瘤细胞凋亡，而且在凋亡的肿瘤细胞旁可见淋巴细胞的聚集。结论： ＨＳＶ－ｔｋ、Ｂ７联合基因治疗可能具有诱发肿瘤细胞凋亡和增强机体抗肿瘤免疫的双重作用。
Objective: To investigate the synergy of HSV-tk gene and B-cell activation antigen (B7) combined gene therapy for breast cancer. METHODS: After tumorigenicity of SHZ-88 breast cancer cells in SD suckling mice, they were randomly divided into control group, tk group, B7 group, and tk+B7 group, with 10 mice in each group. After 3 weeks, tumor cells were injected with 0.2 ml of empty vector or SHZ-88 cells transfected with GcTKpSN, pB7SN, and GcTKpB7SN gene, respectively, and about 5×10 6 cells were intraperitoneally injected with 50 μg·kg -1 ·d - 1 . Six days after injection of hydroxymethyl acyclovir (GCV), the specimens were observed by transmission electron microscopy. RESULTS: A large number of breast cancer cell apoptosis were observed in the tk group. Lymphocyte aggregation was observed around the tumor cells in the B7 group. In the mixed group, not only was the tumor cell apoptosis observed, but also lymphocyte aggregation was observed beside the apoptotic tumor cells. Conclusion: HSV-tk and B7 combined gene therapy may have dual effects of inducing tumor cell apoptosis and enhancing anti-tumor immunity.