微泡造影剂超声辐照介导自杀基因系统治疗肝癌实验研究

Ultrasound microbubble contrast agent mediated suicide gene transfection in the treatment of hepatic cancer

目的探讨微泡造影剂超声辐照介导自杀基因系统治疗体内肝癌肿瘤的作用。方法采用小鼠肝癌瘤体内直接注射KDR-TK、AFP-TK基因和微泡造影剂SonoVue后加以超声辐照的介导方式,并通过给予GCV和5-FC两种前药,观察肿瘤生长体积、抑瘤率、生存时间、肿瘤细胞凋亡指标。结果 (1)治疗组小鼠皮下肝癌移植瘤体生长体积与对照组之间差异无统计学意义,但治疗组的抑瘤率有增加,与对照组比较差异有统计学意义(P<0.05);(2)治疗组与对照组小鼠生存时间差异均无统计学意义(P>0.05);(3)治疗组诱导肿瘤组织内的细胞凋亡增多,与对照组差异有统计学意义(P<0.05);(4)各组除针道外,肿瘤组织内未见明显坏死。结论微泡造影剂超声辐照介导自杀基因治疗系统具有抑制小鼠体内肝癌实体瘤的生长速率的趋势,可能的机制是诱导肿瘤细胞凋亡。

Objective To investigate the ultrasound microbubble contrast agent mediated suicide gene transfec- tion in the treatment of hepatic cancer. Methods Intra - tumor injection of KDR - TK, AFP - TK and microbubble con- trast agent was performed followed by ultrasound treatment and administration of prodrugs （ GCV and 5 - FC） in mice. The tumor volume, tumor inhibition rate, survival time and apoptosis of tumor cells were determined. Results The size of subcutaneous hepatic cancer in mice receiving treatment was comparable to that in control group, but the tumor inhibition rate in treatment group was significantly higher than that in control group （ P 〈 0. 05 ）. The survival time was similar be- tween the two groups （ P 〉 0. 05 ）. The apoptotic cells in treatment group was significantly increased when compared with that in control group （ P 〈 0. 05 ）. Evident tumor necrosis was absent in both groups, except for at the needle tract. Con- clusion Ultrasound therapy following injection of suicide genes and microbubble contrast agents can inhibit the cancer growth in vivo, which may be attributed to the induction of apoptosis of cancer cells.