Smac基因转染对卵巢癌SKOV3/DDP裸鼠移植瘤顺铂敏感性及微血管生成的影响

目的:探讨转染Smac基因对卵巢癌SKOV3/DDP裸鼠移植瘤顺铂敏感性及微血管生成的影响。方法:建立卵巢癌SKOV3/DDP裸鼠移植瘤模型,随机分为5组,分别给予不同药物干预:(1)对照组:移植瘤内注射生理盐水;(2)DDP组:腹腔内注射顺铂;(3)空质粒+DDP组:移植瘤内注射空质粒,24h后腹腔内注射顺铂;(4)Smac组:移植瘤内注射Smac重组质粒;(5)Smac+DDP组:移植瘤内注射Smac重组质粒,24h后腹腔内注射顺铂。顺铂浓度为0.5mg/m1,给药剂量按3mg/kg计算。观察各组裸鼠移植瘤体积变化,计算抑瘤率。TUNEL法检测移植瘤组织标本的凋亡指数,免疫组化法检测CD34并计算微血管密度(MVD)。结果:Smac+DDP组的移植瘤体积最小,平均抑瘤率72.94%,与其他组比较差异有统计学意义(P0.05)。对照组、DDP组、空质粒+DDP组、Smac组、Smac+DDP组的凋亡指数分别为(19.90±3.18)%,(21.82±4.40)%,(22.64±3.81)%,(30.23±4.06)%,(48.59±4.47)%,MVD计数分别为(24.8±5.36),(21.2±3.11),(19.8±3.70),(14.4±3.85),(11.6±2.70)。其中,Smac+DDP组的凋亡指数最高,MVD最低,与其他组比较差异有统计学意义(P0.05)。结论:Smac基因转染可增强卵巢癌耐药移植瘤对顺铂的敏感性,同时减少微血管生成。

The effect of Smac on the sensitivity of nude mice xenografis of DDP-resistant ovarian cancer to cisplatin and angiogenesis

Objective:To investigate the effect of Smac on the sensitivity of nude mice xenografis of DDP-resistant ovarian cancer to cisplatin and angiogenesis. Methods:Human cis-plantin-resistance ovarian cancer models transplanted subcutaneously in nude mice were estab-lished,and divided into 5 groups to do drug intervention:N. S. , DDP, empty plasmids and DDP,recobinant Smac plasmids as well as Smac plasmids and DDP were injeccted into the tumor-bearing mice with Lipofect to interfere with the growth of translanted tumor. The effect on the volume and inhibitory rate of the tumor were observed. The cell apoptosis in tumor tissues was detected by TUNEL. Immunohistochemistry was employed for calculating microvascular density( MVD) . Results:The tansplanted tumor volume in group Smac+DDP were significantly smaller than the other groups,the tumor inhabition rates of it was 72. 94%(P<0. 05). Each group,s apoptosis index detected by TUNEL was(19. 90±3. 18)%,(21. 82±4. 40)%,(22. 64 ±3. 81)%,(30. 23±4. 06)%,(48. 59±4. 47)%,MVD was(24. 8±5. 36),(21. 2±3. 11), (19. 8±3. 70),(14. 4±3. 85),(11. 6±2. 70). The apoptosis index of group Smac+DDP were highest and the MVD of it was lower than other four groups ( P<0 . 05 ) . Conclusions:Smac could enhance the sensitivity of ovarian carcinoma xenograff to cisplatin chemotherapy,and also can suppress tumor angiogenesis.