多西他赛固体脂质纳米粒抗乳腺癌效果及机制研究  

Anti Breast Cancer Effect and Mechanism of Docetaxel Solid Lipid Nanoparticles

作　　者：叶鹏[1] 陈莉[1] 李丹[1] 施偲[1] 

机构地区：[1]武汉大学人民医院药学部,湖北武汉430060

出　　处：《现代生物医学进展》2016年第33期6429-6432,6417,共5页Progress in Modern Biomedicine

摘　　要：目的:探讨多西他赛固体脂质纳米粒抗乳腺癌效果及机制研究。方法:本实验采用MTT法考察了多西他赛固体脂质纳米粒对人乳腺癌MCF-7细胞增殖的抑制作用,采用流式细胞术检测多西他赛固体脂质纳米粒对MCF-7肿瘤细胞凋亡作用,并进一步应用Western-Blot印迹法观察多西他赛固体脂质纳米粒对MCF-7细胞中Src、E-cadherin、β-catenin蛋白表达的影响,探索了其抗乳腺肿瘤的作用机制。结果:多西他赛固体脂质纳米粒能够显著抑制人乳腺癌MCF-7肿瘤细胞的增殖,且浓度越高,抑制率越大(P<0.05)。经25、50、100μg/m L多西他赛固体脂质纳米粒制剂作用24 h后,人乳腺癌细胞MCF-7的凋亡率分别为14.56%、21.21%、29.94%,细胞凋亡率随着药物浓度的增加而增加,且各实验组间比较有显著性差异(P<0.05)。人乳腺癌MCF-7肿瘤细胞经不同浓度的多西他赛固体脂质纳米粒处理后,细胞中E-cadherin蛋白表达显著升高,Src、β-catenin蛋白表达显著降低,且呈现出明显的剂量依赖性。结论:多西他赛固体脂质纳米粒能够抑制人乳腺癌MCF-7细胞增殖,促进其凋亡,可能与下调β-catenin蛋白的表达,上调E-cadherin蛋白表达以及抑制Src激酶活性有关。Objective： To investigate the antitumor effect and the mechanism of docetaxel loaded solid lipid nanoparticles on breast cancer cells. Methods： Inhibitory effect of docetaxel loaded solid lipid nanoparticles on the proliferation of human breast cancer cell line MCF-7 was tested by MTT method, apoptosis of tumor cells was detected by flow cytometry, the expression of Src, E-cadherin and β-Catenin protein in MCF-7 cells cultured with docetaxel loaded solid lipid nanoparticles were tested by Western-Blot method. Results：Docetaxel loaded solid lipid nanoparticles had strong inhibition on the proliferation of human breast cancer MCF-7 tumor cells. After incubation with 25, 50, 100 μg/ml of docetaxel solid lipid nanoparticle preparation for 24 h, human breast cancer MCF-7 cell line showed different apoptosis rates of 14.56%, 21.21%, 29.94%, cell apoptosis increased with drug concentration and there was a significant difference between any two experimental groups（P〈0.05）. The Src, E-cadherin and β-Catenin protein expression in MCF-7 cells treated with different concentrations of docetaxel loaded solid lipid nanoparticles showed a significant dose dependent effect. As the drug concentration increased, the E-cadherin protein expression level also rose significantly, but the Src and β-catenin protein expression levels dropped significantly. Conclusion： Docetaxel loaded solid lipid nanoparticles can inhibit the proliferation of breast cancer cells. The mechanism may be related to up-regulation of the expression of E-cadherin protein, down-regulation of the expression of β-catenin pro- tein, and the inhibition of Src kinase activity.

关 键 词：多西他赛固体脂质纳米粒 乳腺癌 抗肿瘤 体外细胞毒作用 机制研究 

分 类 号：R737.9[医药卫生—肿瘤]