Ki67启动子调控增殖腺病毒对人黑素瘤裸鼠移植瘤的生长抑制作用

Inhibitory effect of conditionally replicative adenovirus carrying Ki67-promoter on the growth of human malignant melanoma xenograft in nude mice

目的:评价携带Ki67启动子的条件增殖型腺病毒Ki67-ZD55对人A375细胞恶性黑素瘤裸鼠移植瘤模型的疗效。方法:将裸鼠黑素瘤移植瘤模型鼠随机分为3组,每组10只,分别给予PBS、ZD55-EGFP、Ki67-ZD55治疗后,测量肿瘤生长体积,免疫印迹法检测肿瘤组织E1A蛋白的表达,TUNEL法检测肿瘤组织凋亡,免疫组化法检测E1A、Bcl-2、BAX蛋白的表达。结果:Ki67-ZD55组的肿瘤生长速度明显慢于PBS组和ZD55-EGFP组,肿瘤生长曲线显示Ki67-ZD55具有抑制肿瘤生长的效果(P<0.05);TUNEL检测显示Ki67-ZD55治疗组的凋亡指数明显高于PBS组(P<0.05)和ZD55-EGFP组(P<0.05);免疫组化显示Ki67-ZD55组可以上调BAX、下调Bcl-2的表达。结论:Ki67-ZD55可以明显抑制人A375黑素瘤细胞裸鼠移植瘤的生长。

Objective： To investigate the effect of Ki67- ZD55 carrying Ki67- promoter （Ki67- ZD55） on hu- man A375 melanoma xenografts in nude mice. Method： Human A375 melanoma cells were transplanted into nude mice. Thirty mice were randomly divided into 3 groups： PBS group, Ki67 - ZD55 group and ZD55 - EGIZP group. After treatments, the tumor volume was measured. The expression of E1A protein was detected by Western Blot; Apoptosis of cancer tissue in each group was performed by TUNEL assay; Immunohistochemistry staining was used to detect E1A、Bcl - 2 and BAX. Results： Tumor growth in Ki67 - ZD55 group was significantly slower compared with those in PBS group and ZD55 - EGFP group. The curve of tumor growth showed that the tumor growth in Ki67 - ZD55 group was inhibited significantly （ P 〈 0.05） ; the inhibition effect of Ki67 - ZD55 group was more significant- ly compared with PBS group（ P 〈 0.05）; TUNEL assay showed that apoptosis index in the Ki67 - ZD55 group was significantly higher than that in PBS group （ P 〈 0.05） or ZD55 - EGFP group （ P 〈 0.05） ; Immunohistochemistry staining revealed that Ki67 - ZD55 enhanced expression of BAX and decreased expression of Bcl - 2. Conclusion： Ki67 - ZD55 can suppress the growth of human A375 melanoma cells in nude mice.