PEG修饰的索拉非尼脂质体联合核转录因子NF-κB抑制剂的抗肿瘤活性研究

Study on the Anti-tumor Activity of PEG-modified Liposomes Combined with Sorafenib Nuclear Transcription Factor NF-κB Inhibitors

关键词:  索拉菲尼  脂质体  核转录因子  抗肿瘤

Key words:  sorafenib  liposomes  nuclear transcription factor  anti-tumor

摘要:

目的 考察PEG修饰的索拉菲尼脂质体联合核转录因子NF-κB抑制剂吡咯烷二硫代氨基甲酸（PDTC）的体内外抗肿瘤活性。方法 采用薄膜分散法制备PEG修饰的索拉菲尼脂质体，体外细胞毒性试验考察游离药物与脂质体的抗肿瘤作用。同时以5~7周龄SPF裸鼠为研究对象，建立体内肿瘤模型，通过测量裸鼠体质量、肿瘤质量与体积变化情况评价药物的抗肿瘤作用，并采用免疫印迹检测手段评价索拉菲尼脂质体及不同浓度的PDTC联合促凋亡、抗肿瘤作用。结果 采用最优处方制备的索拉菲尼脂质体包封率高、分布均匀，体外抗结肠直肠癌细胞SW480作用较游离药物强。体内动物试验结果显示索拉菲尼脂质体联合使用PDTC组能显著降低肿瘤的生长速度，具有较高的抑制肿瘤和促凋亡作用，免疫印迹结果亦进一步证实了二者的联合应用能更强地促进肿瘤细胞凋亡。结论 通过体内外试验，证实了PEG修饰的索拉菲尼脂质体联合核转录因子NF-κB抑制剂PDTC能显著提高药物的抗肿瘤和促凋亡作用，可为索拉菲尼新型载药系统的深入研究提供参考。

Abstract:

OBJECTIVE To investigate the anti-tumor activity of PEG-modified liposomes combined with sorafenib nuclear transcription factor NF-κB inhibitors PDTC in vivo and in vitro. METHODS The PEG-Sora-LPs were prepared by using thin-film methods. Cytotoxicity assays in vitro were applied to investigate the anti-tumor effect of free drug and liposomes. The in vivo tumor model was established based on the 5-7 weeks old SPF nudes. The weight of the nudes, the weight and size of tumors were measured to assess the anti-tumor effects. And Western blot detection means were applied to evaluate the pro-apoptotic and anti-tumor effects PEG-Sora-LPs combined with varying concentrations of PDTC. RESULTS The optimal prescription of PEG-Sora-LPs were prepared with high encapsulation efficiency and were evenly distributed. The anti-tumor effects of PEG-Sora-LPs were stronger than free drug in SW480 cells in vitro. In vivo animal studies showed that in combination with PEG-Sora-LPs, PDTC could significantly reduce the rate of tumor growth, with higher tumor inhibition and induce apoptosis functions. Western blot analysis also confirmed the joint application of these two had stronger effects to promote tumor cell apoptosis. CONCLUSION PEG-modified liposomes combined with sorafenib nuclear transcription factor NF-κB inhibitor PDTC can significantly increase the anti-tumor and pro-apoptotic effects by in vivo and in vitro experiments. This study can provide a reference for the investigation of sorafenib new drug system.