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目的制备载内皮抑素(endostain,ES)壳聚糖纳米粒(endostatin-loaded chitosan nanoparticles,ES-NPs),并探讨其联合顺铂(cisplatin,DDP)对小鼠Lewis肺癌模型的治疗作用。方法采用离子凝胶法制备ES-NPs,并对其形态及基本性质进行研究。建立小鼠Lewis肺癌皮下移植瘤模型,按随机数字表法分为对照组、ES组、DDP组、ES-NPs组、ES+DDP组、ES-NPs+DDP组。各组给药后,动态测量小鼠移植瘤体积,免疫组化检测移植瘤组织中微血管密度(microvessel density,MVD),ELISA检测小鼠血清中内皮抑素和VEGF水平。结果制备的ES-NPs具有合适的粒径和较高的包封率,在体外具有明显缓释性,7 d累积释放量达(60.22±2.58)%。当ES-NPs与DDP联合时,能明显抑制肺癌移植瘤生长,观察结束时,ES-NPs+DDP组的抑瘤率为76.47%,明显高于ES+DDP组及其余各组(P<0.05)。同时,免疫组化和ELISA检测结果证实了ES-NPs与DDP联合对肿瘤血管具有较强的抑制作用。结论内皮抑素纳米粒联用DDP可增强对小鼠Lewis肺癌移植瘤的抗瘤效果。
OBJECTIVE To prepare endostatin-loaded chitosan nanoparticles (ES-NPs) and investigate the therapeutic effect of cisplatin (DDP) on Lewis lung carcinoma in mice. Methods ES-NPs were prepared by ion-gel method and their morphology and basic properties were studied. The subcutaneous xenograft models of Lewis lung cancer in mice were established and divided into control group, ES group, DDP group, ES-NPs group, ES + DDP group and ES-NPs + DDP group by random number table. After administration of each group, the volume of tumor was measured dynamically in mice, the microvessel density (MVD) in the tumor tissue was detected by immunohistochemistry and the level of endostatin and VEGF in the serum was detected by ELISA. Results The prepared ES-NPs had suitable particle size and high entrapment efficiency. The ES-NPs had a sustained release in vitro and reached a cumulative release of (60.22 ± 2.58)% after 7 days. When combined with DDP, ES-NPs could significantly inhibit the growth of lung cancer xenografts. At the end of observation, the inhibition rate of ES-NPs + DDP group was 76.47%, which was significantly higher than ES + DDP group and other groups (P <0.05 ). Meanwhile, the results of immunohistochemistry and ELISA confirmed that ES-NPs and DDP combined have a strong inhibitory effect on tumor blood vessels. Conclusion Endostatin nanoparticles combined with DDP can enhance the anti-tumor effect of transplanted Lewis lung cancer in mice.