来氟米特对前列腺癌PC3细胞增殖与凋亡的影响  

The effects of Leflunomide on cellular proliferation and apoptosis in PC3 cells

作　　者：周华[1] 姜科声[1] 黄巧丽 陈艺成[2] 李彦明[3] 李涛[1] 

机构地区：[1]浙江师范大学化学与生命科学学院,浙江金华321004 [2]浙江大学医学院附属邵逸夫医院,浙江杭州310031 [3]河南大学附属淮河医院,河南开封475000

出　　处：《浙江师范大学学报（自然科学版）》2017年第1期79-84,共6页Journal of Zhejiang Normal University:Natural Sciences

基　　金：国家自然科学基金资助项目(31101057;31470082;81101929);浙江省自然科学基金资助项目(LY14C120001);浙江省公共创新平台实验动物项目(2014C37126);浙江省卫生厅创新平台项目(2015RCA014)

摘　　要：为了研究来氟米特(LEF)对前列腺癌细胞增殖和凋亡的影响,采用前列腺癌细胞株PC3与不同浓度的来氟米特(0,50,100,150μmol·L^(-1))共培养(24,48,72 h),通过CCK-8细胞活力检测实验和克隆形成实验,发现来氟米特抑制PC3细胞增殖,且存在明显的浓度时间依赖性;流式细胞检测表明,来氟米特使PC3细胞发生S期阻滞,并且促进其凋亡;当来氟米特浓度≥150μmol·L^(-1)时,Western Blot实验检测到Caspase-3蛋白发生剪切活化.来氟米特处理可诱导PC3细胞自噬,采用羟氯喹抑制自噬可促进细胞凋亡的发生,提示自噬增强了细胞抗凋亡能力.研究表明,来氟米特可抑制PC3细胞的增殖,诱导其凋亡,可能对前列腺癌有潜在的治疗作用.Leflunomide （LEF）, an immunosuppressive drug, was generally used in the treatment of rheumatoid arthritis. Recently, increasing evidences indicated that LEF had an effective anti-proliferative effect on various tumors. To investigate the effect of LEF in prostatic cancer cells, prostatic cancer cell line PC3 was trea-ted with solutions of LEF （0, 50, 100 and 150 μmol·L^-1） and cultured in varied duration of time （24, 48 and 72 h）. CCK-8 and cell clone forming experiments showed that when the concentration was ≥ 150 μmol·L^-1 LEF significantly inhibited cell growth in a time- and dose-dependent manner. Annexin V-FITC/PI staining assay revealed that LEF induced S-phase cell cycle arrest, and enhanced cell apoptosis via modulation of Caspase-3 expression as shown by Western blotting experiments. Moreover, LEF could induce autophagy of PC3 cells, while hydroxychloroquine （HCQ） could enhance LEF-induced apoptosis by inhibiting autophagy. Taken together, LEF inhibited proliferation and promoted apoptosis of the PC3 cells.

关 键 词：来氟米特 前列腺癌 增殖 凋亡 自噬 

分 类 号：Q291[生物学—细胞生物学]