靶向肿瘤新生血管唑来膦酸阳离子隐形脂质体抗肿瘤作用的研究

Anti-tumor effects of zoledronic acid-loaded stealth cationic liposome by targeting tumor angiogenesis

目的:研究APRPG(Ala-Pro-Arg-Pro-Gly)修饰的隐形唑来膦酸阳离子脂质体对荷前列腺癌PC-3裸鼠的抗肿瘤作用。方法:构建荷前列腺癌PC-3裸鼠模型,比较研究唑来膦酸阳离子脂质体、APRPG修饰的隐形唑来膦酸阳离子脂质体对肿瘤体积增长的抑制作用,计算肿瘤抑制率,并通过免疫组化实验分析其对肿瘤相关因子血管内皮生长因子(VEGF)和分化抗原簇44(CD44)表达的影响。结果:唑来膦酸阳离子脂质体、APRPG修饰的隐形唑来膦酸阳离子脂质体对荷前列腺癌PC-3裸鼠的肿瘤抑制率分别为31.81%、68.18%,后者的肿瘤抑制率明显高于前者(P<0.05),免疫组化结果显示VEGF和CD44蛋白在模型对照组中表达呈强阳性,在唑来膦酸阳离子脂质体组中呈中度阳性表达,而在APRPG修饰的隐形唑来膦酸阳离子脂质体中表达较为微弱。结论:APRPG修饰的隐形唑来膦酸阳离子脂质体对前列腺癌PC-3裸鼠具有更强的肿瘤抑制率。

AIM： To investigate the anti-tumor effect of APRPG modified zoledronic acid-loaded stealth cationic liposomes in nude mice bearing PC-3 prostate cancer. METHODS： Prostate cancer cell PC-3 beared nude mice model was constructed, growth inhibition of tumor volume between zoledronic acid cationic liposome and APRPG modificated zole- dronic acid-loaded stealth cationic liposomes was compared, and the tumor inhibition rate was calcu- lated. Immunohistochemistry analysis was used to detect the effect on expression of VEGF and CD44. RESULTS：The tumor inhibition rate of zoledronic acid cationic liposome and APRPG modificated zole- dronic acid-loaded stealth cationic liposomes were 31.81%, 68.18% , respectively, the tumor inhibition rate of the latter was significantly higher than that of the former （ P 〈 0.05 ） , immunohistochemi- cal results showed that VEGF and CD44 protein ex- pression was strong positive in the model control group, in zoledronic acid cationic liposome group, it showed a moderate positive expression, and in AP- RPG modificated zoledronic acid-loaded stealth cat- ionic liposomes group, the expression was very weak. CONCLUSION： stealth liposome can exert in PC-3 nude mice. The APRPG modified a stronger inhibition effect