靶向熊果酸脂质纳米粒抗宫颈癌的作用研究

Anti-cervical cancer effect of targeting ursolic acid lipid nanoparticles

目的探讨靶向熊果酸脂质纳米制剂抗宫颈癌的作用效果。方法利用新型靶向性功能材料叶酸-CONH-聚乙二醇-NH-胆固醇合成靶向熊果酸脂质纳米粒,采用MTT法对比靶向熊果酸脂质纳米粒的人宫颈癌HeLa细胞和宫颈正常鳞状上皮细胞的增殖抑制作用的差异性;用流式细胞术考察其促细胞凋亡作用;应用蛋白免疫印迹(Western blotting)检测Bcl-2、Bax、Livin及Caspase-3的蛋白表达,用实时荧光定量-聚合酶链式反应(q RT-PCR)检测基因表达,探索靶向熊果酸脂质纳米粒抗宫颈肿瘤的作用机制。初步考察靶向熊果酸脂质纳米粒在荷瘤鼠体内的抗肿瘤作用。结果靶向熊果酸脂质纳米粒对HeLa细胞具有显著的细胞增殖抑制及促细胞凋亡作用;使细胞中Livin、Bcl-2基因或蛋白表达增加,Caspase-3、Bax基因或蛋白表达减少;体内抑瘤效率高于普通熊果酸脂质纳米粒。结论靶向熊果酸脂质纳米粒可有效传输药物至肿瘤组织,抑制细胞的增殖,促使其凋亡,具有一定的体内抗肿瘤效果。

Objective To investigate the effect of targeting ursolic acid lipid nanoparticles on cervical cancer. Methods In this study, a novel targeted functional material, folate-CONH-polyethylene glycol-NH-cholesterol, was firstly used to synthesize targeted lipid nanoparticles. MTT assay was used to detect and compare the difference of its inhibition on the proliferation of human cervical cancer HeLa cells and normal cervical squamous epithelial cells. The flow cytometry was then used to investigate the pro-apoptotic effect of ursolic acid lipid nanoparticles on HeLa cells. The effects of ursolic acid lipid nanoparticles on the protein expressions of Bcl-2, Bax, Livin, and Caspase-3 were detected by Western blotting and gene expressions were detected by qRT-PCR, and the mechanism of its targeted anti-cervical tumor was explored. Finally, the anti-tumor effect in tumor-bearing mice was investigated. Results The targeted ursolic lipid nanoparticles showed significant inhibition of cell proliferation and apoptosis in HeLa cells, which may be associated with down-regulating the expression of Livin and Bcl-2 protein, and up-regulating the expression of Caspase-3 and Bax protein. In vivo tumor inhibition efficiency was higher than other groups. Conclusion Targeted lipid nanosystem can effectively deliver drugs to tumor tissues, inhibit the proliferation of cells, and promote their apoptosis, which has certain anti-tumor efficiency in vivo.