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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。
Objective To investigate the in vitro and in vivo antitumor activity of sorafenib liposome encapsulated with PEG-modified and NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). Methods PEG modified Sorafenib liposomes were prepared by membrane dispersion method. The antitumor effects of free drugs and liposomes were investigated in vitro cytotoxicity test. At the same time, 5-7-week-old SPF nude mice were selected as the research object to establish the tumor model in vivo. The anti-tumor effect of the drug was evaluated by measuring the body weight, tumor mass and volume changes in nude mice. The immunofluorescent staining Liposomes and different concentrations of PDTC combined apoptosis, anti-tumor effect. Results The sorafenib liposomes prepared by optimal prescription had high encapsulation efficiency and uniform distribution, and the anti-colorectal cancer SW480 cells in vitro had stronger effect than free drug. In vivo animal experiments show that the combination of sorafenib liposomes PDTC group can significantly reduce tumor growth rate, with higher inhibition of tumor and pro-apoptotic effect, Western blotting results also further confirmed the combination of the two can be more Strongly promote tumor cell apoptosis. Conclusion In vitro and in vivo experiments demonstrated that PEG-modified sorafenib liposome combined with nuclear factor NF-κB inhibitor PDTC can significantly enhance the antitumor and proapoptotic effects of the drug, which may be a new drug for sorafenib System in-depth study to provide a reference.