新型左旋棉酚纳米微球的制备及在体外抑制人前列腺癌PC-3细胞生长的研究  

Preparation of a novel nanoparticles of (-)- gossypol and growth inhibition on human prostate cancer PC-3 cells in vitro

作　　者：张献清[1] 詹永华[2] 穆士杰[1] 陈晨[1] 刘志新[1] 胡兴斌[1] 安群星[1] 黄晓峰[3] 

机构地区：[1]第四军医大学西京医院输血科,陕西西安710032 [2]西安电子科技大学生命科学学院,陕西西安710071 [3]第四军医大学中心实验室,陕西西安710032

出　　处：《现代肿瘤医学》2012年第3期489-492,共4页Journal of Modern Oncology

摘　　要：目的:研究负载左旋棉酚的单甲氧基聚乙二醇-马来酰亚胺(mPEG-mal)纳米微球的体外抗肿瘤活性,并对其机理进行探讨。方法:采用乳化-挥发法制备负载左旋棉酚的纳米微球,在人前列腺癌PC-3细胞及人前列腺细胞RWPE-1细胞株上分析空白微球的毒性,以MTT法、AO染色、透射电镜及半定量RT-PCR检测Bcl-2及Bak mRNA的表达等方法评价其在体外对前列腺癌细胞株PC-3的抗肿瘤活性,并与左旋棉酚裸药进行比较。结果:左旋棉酚载药微球对体外培养的前列腺癌细胞生长的抑制与裸药相似,并呈剂量-时间依赖性,纳米微球可以诱导PC-3细胞发生典型的凋亡形态学改变,使Bcl-2 mRNA表达水平降低,Bak mRNA表达水平升高,空白微球在高浓度时,对于肿瘤细胞系及人前列腺RWPE-1细胞株均无明显毒性。结论:左旋棉酚纳米微球具有良好的抗肿瘤活性,载体无毒,具有良好的生物相容性,能诱导前列腺癌细胞的体外凋亡,是一种具有潜力的抗肿瘤纳米药物。Objective：To investigate the antitumor effects and the possible mechanism of（-）-gossypol-loaded nanoparticles with mPEG-maleimide in vitro.Methods：The（-）-gossypoi loaded nanoparticles were prepared by emulsion-evaporation method.The toxicity of blank nanoparticle was measured on human prostate cancer PC 3 cells and human prostate RWPE-1 cells.The antitumor effects on PC-3 cells of nanoparticles were evaluated by MTT assay,AO staining and transmission electron microscopy in vitro,a nd then compared with free（-）-gosssypol.The Bcl-2 and Bak mRNA level were measured by semiquantitative RT-PCR.Results：The growth inhibition activities of（-）-gossypol-loaded nanoparticles were in a dose-and time-dependent manner and similar to that of free（-）-gossypol.The nanoparticles can induce morphological change of apoptosis on PC-3 cells and down regulate Bcl-2 mRNA and up-regulate Bak mRNA level.Blank nanoparticals have no obvious toxicity on PC-3 cells and RWPE-1 cells in high dose.Conclusion：The（-）-gossypol loaded nanoparticles had favorable antitumor activity and no toxicity.It can induce apoptosis of prostate cancer cells and it would be a potent antitumor nanodrug.

关 键 词：左旋棉酚 纳米粒子 凋亡 前列腺癌 

分 类 号：R737.25[医药卫生—肿瘤] R73-34[医药卫生—临床医学]