紫杉醇对卵巢癌细胞作用的浓度依赖性及其机制探讨  

Concentration-Dependent Effects of Taxol to Ovarian Cancer Cells and the Related Mechanisms

作　　者：王丽[1,2] 杨宾烈[2] 郝星[1] 马湘一[1] 翁丹卉[1] 廖书杰[1] 卢运萍[1] 王世宣[1] 于洪涛 马丁[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院妇产科,武汉430030 [2]上海市浦东新区公利医院妇产科,上海200135 [3]德克萨斯州西南医学中心药理学与分子生物学系,达拉斯,美国75390-9041

出　　处：《华中科技大学学报（医学版）》2008年第2期236-238,250,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：海外青年学者合作研究基金资助项目(No.30528012)

摘　　要：目的探讨不同浓度紫杉醇对卵巢癌细胞发挥抗癌效应的内在机制。方法以0．01、0．1、1、10、50μmol／L紫杉醇作用于人卵巢癌细胞系A2780，采用碘化丙啶（PI）单染法流式细胞术检测不同浓度紫杉醇作用下细胞周期的变化情况。进而对细胞进行同步化处理，采用PI单染法流式细胞术分析低浓度（0．01μmol／L）紫杉醇对细胞周期的影响；Annexin V／PI双染法流式细胞术分析高浓度（50μmol／L）紫杉醇对A2780细胞坏死的影响。结果①紫杉醇浓度为0．1、1、10μmol／L时，G2／M期细胞比例明显高于0．01μmol／L组（P〈0．01）和50μmol／L组（P〈0．01）。②A2780细胞经同步化处理后给予0．01μmol／L紫杉醇，经过一个细胞倍增时间未观察到G0／G1期阻滞。③0．01μmol／L组，1μmol／L组坏死细胞比例明显低于50μmol／L组（P〈0．01）。结论在0．1～10μmol／L的浓度范围内，紫杉醇可能通过诱导G2／M期阻滞使卵巢癌细胞发生凋亡，浓度为0．01μmol／L时紫杉醇诱导凋亡与G0／G1期或G2／M期阻滞均无关，浓度为50μmol／L时紫杉醇可能主要通过诱导细胞坏死发挥抗癌效应。Objective To investigate the anti-tumor effect of taxol at different concentrations on ovarian cancer cells and the internal mechanisms. Methods （1） Human ovarian cancer cell line A2780 cells were exposed to 0.01, 0.1, 1, 10, 50 μmol/L taxol. By using propidium iodide （PI） staining and fluorescence-activated cell sorting （FACS）, the changes in the cell cycle were examined after the A2780 cells were treated with differenct concentrations of taxol; （2） After being synchronised at G1/S with thymidine, A2780 cells were exposed to 0.01 μmol/L taxol for 12 and 24 h, followed by being stained with PI and analyzed with FACS for cell cycle distribution; （3） By using Annexin V/PI staining and FACS, the effect of 50 μmol/L taxol on the necrosis of A2780 cells was analyzed. Results （1） The percentage of G2/M cells treated with 0.1, 1 and 10 μmol/L taxol was significantly higher than that of G2/M cells treated with 0.01 or 50 μmol/L taxol. （2） No G0/G1 arrest was observed after synchronized A2780 cells were treated with 0.01 μmol/L taxol for a double time; （3） The ratio of necrotic cells in A2780 cells treated with 50 μmol/L taxol was statistically higher than that in those exposed to 1 or 0.01 μmol/L taxol. Conclusion 0.1, 1 and 10 μmol/L taxol induces apoptosis of ovarian cancer cells dominantly through G2/M arrest-dependent mechanisms. 50 μmol/L taxol exerts its anti-cancer effect through inducing necrosis, while 0.01 μmol/L taxol induces apoptosis through neither G0/G1 arrest nor G2/M block.

关 键 词：卵巢癌 紫杉醇 细胞周期 细胞凋亡 

分 类 号：R737.31[医药卫生—肿瘤]