吡柔比星联合苏拉明对人膀胱癌裸鼠移植瘤的实验研究

Inhibitory Effects of Pirarubicine Combined with Suramin on T24 Bladder Carcinoma in Nude Mice

目的:研究吡柔比星联合苏拉明对人膀胱癌裸鼠移植瘤的影响。方法:将24只BALB/c裸鼠T24人膀胱癌细胞接种后随机分为对照组、吡柔比星组、苏拉明组、吡柔比星和苏拉联合用药组(联合治疗组)(每组n=6)给予不同处理,观察各组裸鼠移植瘤用药后的生长曲线变化。4周后处死取出肿瘤组织:测量肿瘤大小、重量并计算抑瘤率;采用免疫组化检测肿瘤组织微血管密度(Microvessel density,MVD)、流式细胞分析仪细胞凋亡、反转录酶-聚合酶链锁反应(Reverse transcription-polymerase chain reaction,RT-PCR)检测各组肿瘤组织中成纤维细胞生长因子(Basic fibroblast growth factor,b FGF)和血管内皮生长因子(Vascular endothelial growth factor,VEGF)m RNA的表达。结果:联合治疗组肿瘤生长曲线明显慢于其它各组;联合治疗组抑瘤率(56.03%)明显高于吡柔比星组(30.12%)、苏拉明组(35.32%)抑瘤率(P<0.05);吡柔比星组、苏拉明组及联合治疗组MVD值分别为13.01±2.98、11.32±2.11、8.82±0.77,与对照组MVD(19.88±2.62)相比明显下降(P<0.05);流式细胞仪检测凋亡显示联合治疗组细胞凋亡率(38.57±3.98)明显高于吡柔比星组(14.78±2.95)、苏拉明组(20.92±3.67)及对照组(10.03±1.34)(P<0.05);RT-PCR结果显示,联合治疗组b FGF和VEGF表达量明显降低。结论:吡柔比星和苏拉明联合应用在体内能抑制膀胱癌裸鼠移植瘤的生长、诱导肿瘤细胞的凋亡和抑制肿瘤血管生成。

Objective： To evaluate the inhibitory effect of pirarubicine（THP） combined with suramin on T24 bladder carcinoma in nude mices. Methods： 24 BALB/c nude mice with T24 tumor cells inoculation were randomly divided into control group, THP group,suramin group, THP and suramin group（combined treatment group）（all n=6）. The changes of growth curve were measured. After four weeks, observation, the mice were sacrificed and the tumors were dissected to measure size, weight and tumor inhibition rate. The microvessel density（MVD） were analysed by using CD34 immunohistochemistry and cell apoptosis were detected by using flow cytometry. Finally, the expression of basic fibroblast growth factor（b FGF） and vascular endothelial growth factor（VEGF） were measured by reverse transcription-polymerase chain reaction（RT-PCR）. Results： Tumor growth curve of combined treatment group was obviously slower than that of the other groups. The tumor inhibition rate of combined treatment group was 56.03%, which was significant significance than that in THP group（30.12%） and suramin group（35.32%）（P〈0.05）. The MVD in THP, suramin and combination groups were 13.01 ±2.98, 11.32 ±2.11, and 8.82 ±0.77, respectively, which was decreased compared to that in the control group（19.88 ±2.62）（P〈0.05）. The apoptosis rate in combination group（38.57 ±3.98） was significantly higher than that in THP group（14.78 ±2.95）, suramin group（20.92 ±3.67）, and control group（10.03 ±1.34）（P〈0.05）. The expression of b FGF and VEGF in combined treatment group was decreased than in other groups. Conclusions： THP combined with suramin could inhibit the tumor growth,induce tumor cell apoptosis and suppress angiogenesis in nude mice.