RGD肽联合丝裂霉素C对荷人膀胱癌T24裸鼠肿瘤生长的抑制作用

Inhibitory effect of RGD peptide and Mitomycin C on human bladder cancer T24 xenotransplanted model of nude mice

目的:探讨纤维连接蛋白(FN)拮抗剂精氨酸-甘氨酸-天冬氨酸三肽(RGD)联合丝裂霉素C(MMC)对荷膀胱癌T24裸鼠肿瘤生长的抑制作用。方法:建立荷膀胱癌T24裸鼠模型(n=32)。全部成瘤后随机分为4组:对照组(n=8):瘤体局部注射生理盐水,1次/3d;RGD组(n=8):瘤体局部注射RGD6μg/g,1次/3d;MMC组(n=8):瘤体局部注射MMC2μg/g,1次/3d;RGD+MMC组(n=8):瘤体局部注射RGD6μg/g和MMC2μg/g,1次/3d。连续治疗5周后处死动物,取出肿瘤称重,计算抑瘤率。结果:RGD+MMC、MMC组抑瘤率分别为77.6%和67.4%;与对照组比较差异均有统计学意义(P<0.05);RGD+MMC组、MMC组肿瘤生长速度明显慢于对照组和RGD组;RGD+MMC组、MMC组肿瘤体积分别为(351.4±86.5)mm3及(520.6±121.9)mm3,均明显小于对照组(1613.9±460.2)mm3(P<0.05);RGD+MMC组、MMC组肿瘤重量分别为(366.5±93.4)mg及(534.7±135.6)mg,均明显小于对照组(1639.5±479.2)mg(P<0.05)。结论:FN拮抗剂RGD肽可协同MMC抑制荷膀胱癌T24裸鼠肿瘤的生长;RGD肽联合MMC治疗膀胱移行细胞癌可能有较好的临床应用前景。

Objective：To study the effect of FN antagonist-RGD peptide and MMC on primary tumor growth of human bladder cancer in xenotransplanted model of nude mice. Methods：Xenotransplanted model of a human bladder cancer cell T24 in nude mice was established. Four weeks later, 32 mice were randomly divided into 4 groups： control group（n=8）.. 0.9% NS injected hypodermically every third day; RGD group（n=8）： RGD was injected hypodermically at dose of 6 μg/g every third day; MMC group（n=8） ： MMC was injected hypodermically at dose of 2 μg/g every third day; RGD＋MMC group （n=8）： RGD was injected hypodermically at dose of 6μg/g every third day combined with MMC （2 μg/g）. Five weeks after treatment, tumor weight, size and tumor growth inhibition rate were evaluated respectively. Results：Compared with the untreated controls, growth of the tumor implanted subcutaneously was significantly reduced in size in the mice treated with MMC and RGD＋MMC, with an inhibition rate of 67.4% and 77.6%, respectively （ P 〈0.05）. Tumor size in MMC group and RGD＋MMC group were（520.6± 121.9）mm^3 and （351.4±86.5） mm^3 respectively, significantly smaller than that in control group： （1613.9±460.2） ram3（P〈0.05）. Tumor weight in MMC group and RGD＋MMC group were （534.7± 135.6） mg and （366.5±93.4）mg respectively, significantly lighter than that in control group： （1 639.5 ±479.2）mg（ P 〈0. 05）. There are no statistically significant difference between control group and RGD group in tumor weight and size （ P 〈0.05 respectively）. Conclusions：RGD combined with MMC can induce apoptosis in bladder cancer and has strong inhibitory effect on tumor growth of human bladder cancer implanted in nude mice.