藻蓝蛋白亚基脂质体光动力学抗乳腺癌细胞的实验研究

Photodynamic Experiment of Phycocyanin Subunits Liposomes against Breast Carcinoma

目的:研究PEG修饰的藻蓝蛋白亚基光敏剂长循环脂质体介导的光动力疗法抗乳腺癌的效果。方法:采用薄膜水合-超声分散法制备PEG修饰的藻蓝蛋白亚基脂质体(PEG-PCS-lip),MTT法检测藻蓝蛋白亚基脂质体对MCF-7(人乳腺癌细胞)、MA-782(鼠乳腺癌细胞)的光动力杀伤效果,流式细胞术(FCM)分析其对肿瘤细胞周期的影响,并对乳腺癌模型鼠做PDT治疗。结果:PEG-PCS-lip介导的PDT作用对乳腺癌细胞有良好的光动力疗效,对MCF-7及MA-782细胞IC_(50)(半数抑制浓度)分别为68μg/mL、70μg/mL;FCM的结果显示,当PEG-PCS-lip浓度为50μg/mL时,MCF-7凋亡率约为30.5%;用10 mg/kgPEG-PCS-lip静脉注射荷瘤小鼠,光照剂量为208.2 J/cm^2时,其抑瘤率可达到72%;组织切片观察PDT作用后的肿瘤组织,瘤体中间以细胞凋亡为主,瘤体外周以细胞坏死为主,由血管损伤而形成的空腔增多。结论:PEG-PCS-lip在体外对乳腺癌细胞有良好的光动力杀伤效果。

Objective：To prepare PEG modified Phycocyanin Subunits Liposomes（PEG-PCS-lip） and study its photodynamic therapy（PDT） effects against breast carcinom. Methods： PEG-PCS-Iip was prepared by film dispersion method, and photodynamic therapy effect in vitro was assessed with MTT method, cell apotosis was analyzed by flow cytometry （FCM）. Then we treated the breast tumor bearing mice with photodynamic therapy. Results： In vitro PDT experiment, the IC50 were 68 μg/mL for MCF-7 and 70 μg/mL for MA-782, The apoptosis ratio of MCF-7 reaehed 30.5 %. In vivo experiment, after injection of 10 mg/kg PEG-PCS-lip in breast tumor bearing mouse, the tumor inhibition ratio was 72 % with the irradiation dose of 208.2 J/cm^2. There was obvious differentiation between outside and inside PDT trea-ted tumor： the outside tissue cells showed cellular necrosis and the inside tissue cells exhibited the nuclear change of apotosis. There were more cavities in the tissue as a result of the occlusion of tumor blood vessels. Conclusion：PEG-PCSlip keep the biological activity of phycocyanin subunits very well and enhanced tumor inhibition rate in breast carcinoma. The tumor cell death was due to the occlusion of tumor blood vessels and inducement of cell programmed death in nuclei.