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二乙酰二脱水卫矛醇抑制鸟氨酸脱羧酶活性及机制初探 被引量:3

Inhibition of Diacetyldianhydrogalactitol on Ornithine Decarboxylase Activity and Its Possible Mechanisms
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摘要 目的研究二乙酰二脱水卫矛醇(DADAG)对鸟氨酸脱羧酶(ODC)活性的影响及其对人前列腺癌PC-3M细胞增殖的作用,并初步探讨其可能的分子机制。方法采用酶促反应法测定DADAG对PC-3M细胞中ODC活性的影响,用SRB法观察DADAG对PC-3M细胞增殖的抑制作用,流式细胞术分析DADAG对PC-3M细胞周期的改变,Western blot方法检测DADAG对PC-3M细胞周期相关蛋白Cdc2,CyclinB1,p-Cdc2(Tyr15),Cdc25C和Wee1表达的影响。结果5和10mg·L-1DADAG作用PC-3M细胞24h后,ODC活性的抑制率分别为39.3%和31.1%。SRB结果显示,40mg·L-1DADAG作用PC-3M细胞48和72h后,细胞增殖抑制率分别为34.6%和47.8%,与对照组比较有显著性差异(P<0.05)。细胞周期分析表明,5,10和20mg·L-1DADAG作用48h后,G2/M期细胞百分数为47.4%,62.9%和69.1%。DADAG作用细胞后,Cdc25C的表达下调,而Cyclin B1,p-Cdc2(Tyr15)和Wee1表达上调,Cdc2变化不明显。结论DADAG可降低PC-3M细胞中ODC的活性,并抑制细胞的增殖,使阻滞细胞周期于G2/M期,DADAG的抗肿瘤机制与降低ODC活性,改变p-Cdc2(Tyr15),Cdc25C和Wee1蛋白表达有关。 OBJECTIVE We explored the effects of diacetyldianhydrogalac-titol (DADAG) on ornithine decarboxylase (ODC) activity and the proliferation of PC-3M human prostate cancer cells and investigated its possible molecular mechanisms. METHODS PC-3M cells were treated with DADAG, ODC activity was tested; cell proliferation was evaluated by sulforhodam/ne B (SRB) assay; cell cycle distribution was detected by flow cytometry, the expression of Cdc2, Cyclin B1, p-Cdc2(Tyr15), Cdc25C, and Weel were detected by Western blot. RESULTS When treated with 5 and 10 mg·L^-1 DADAG for 24 h, the inhibition rates of ODC activity were 39.3% and 31.1%, respectively. When treated with 40 mg·L^-1 DADAG for 48 and 72 h, the inhibition rates of PC-3M cells were 34.6% and 47.8%, respectively, which were significantly higher than that of negative control cells (P〈0.05). When treated with 5, 10, 20 mg·L^-1 DADAG for 48 h, PC-3M cells were arrested at G2/M phase at rates of 47.4%, 62.9% and 69.1% .The expression of Cdc25C was down-regulated, and the expression of Cyclin B 1, p-Cdc2(Tyrl 5), and Weel were up-regulated, Cdc2 had no significant variation. CONCLUSION DADAG down-regulates ODC activity, inhibits PC-3M cell proliferation and blocks cell cycle at G2/M phase . The antitumor mechanism of DADAG is related to the decrease of ODC activity and the changes of p-Cdc2(Tyr15), Cdc25C, Weel expression.
出处 《中国药学杂志》 CAS CSCD 北大核心 2009年第12期904-908,共5页 Chinese Pharmaceutical Journal
关键词 二乙酰二脱水卫矛醇 PC-3M细胞 鸟氨酸脱羧酶 细胞周期 细胞周期蛋白 diacetyldianhydrog- alactitol PC-3M cells omithine decarboxylase cell cycle cyclin
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  • 1V. Erdélyi-Tóth,S. Kerpel-Fronius,B. Kanyár,S. Eckhardt. Pharmacokinetic study in a phase I trial with an alkylating agent, diacetyldianhydrogalactitol (DADAG)[J] 1986,Cancer Chemotherapy and Pharmacology(3):257~263

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