8-Br-cAMP联合HSV-TK/GCV治疗舌鳞癌移植瘤的研究

The Combination of 8-Br-cAMP and HSV-TK/GCV System in the Treatment of Tongue Squamous Carcinoma Xenografts

[目的]探讨8-Br-cAMP联合单纯疱疹病毒胸苷激酶基因(HSV-TK)/丙氧鸟苷(GCV)对舌鳞癌移植瘤的治疗作用。[方法]舌鳞癌Tca8113细胞接种于28只裸鼠右侧腋下,随机分成4组进行治疗:对照组,8-Br-cAMP组,HSV-TK/GCV组,8-Br-cAMP联合 HSV-TK/GCV组;观察肿瘤的生长状态、计算抑瘤率和群体倍增时间;观察肿瘤的组织病理学及超微结构改变。[结果]与对照组比较,8-Br-cAMP和HSV-TK/GCV单独应用时肿瘤的生长明显受到抑制(P<0.01),肿瘤的群体倍增时间延长;析出分析显示两者间存在协同的抑瘤作用(P<0.01)。光镜下对照组和8-Br-cAMP组无明显差别,HSV-TK/GCV组和8-Br-cAMP联合HSV-TK/GCV组肿瘤组织中可见囊性变和大片的灶性坏死;透射电镜显示8-Br-cAMP对舌癌细胞具有诱导分化作用。[结论]8-Br-cAMP与HSV-TK/GCV系统具有协同的抑制舌鳞癌移植瘤生长作用。

[Objective] To investigate the therapeutic efficacy of combination therapy with 8-Br-cAMP(8-Bromo3': 5'-cyclic adenosine monophosphate) and herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system in the treatment of tongue squamous carcinoma xenografts. [Methods] Tca8113 cells were inoculated subcutanously in the right flank of BALB/c nude mice. Mice were randomly assigned to 4 groups and treated: Control group, 8-Br-cAMP group, HSV-TK/GCV group, 8-Br-cAMP + HSV-TK/GCV group. Observe the tumor growth and calculate the inhibition rate and tumor doubling time; Observe tumor histopathological changes. Transmission electron microscope was used to analyze the changes of Tca8113 cells after treated with 8-Br-cAMP. [Results] Compared with control group, mice treated with 8-Br-cAMP or HSV-TK/GCV system demonstrated significant tumor regression ( P < 0.01) and prolonged tumor doubling time. Factorial analysis showed that synergetic anticancer effect existed between 8-Br-cAMP and HSV-TK/GCV system. Cyst-formation and substantial tumor necrotic area were observed under light microscope in HSV-TK/GCV group and 8-Br-cAMP + HSV-TK/GCV group. A series of cell morphological changes, such as more tonofil-aments and well-differentiated organelle, were observed after treated with 8-Br-cAMP. [Conclusion] 8-Br-cAMP and HSV-TK/GCV system have synergetic anticancer effect on tongue squamous carcinoma xenografts.