二氢青蒿素联合环氧化酶2抑制剂抗S180肉瘤作用机制研究  

Ation mechanism of dihydroartemisinin combined with COX-2 inhibitor in S180 carcinoma

作　　者：张佳丽[1] 王增[1] 庄蓓蓓[1] 周慧君[1] 

机构地区：[1]浙江大学药学院药理学与毒理学研究室,浙江杭州310058

出　　处：《中国药理学通报》2009年第3期308-312,共5页Chinese Pharmacological Bulletin

基　　金：浙江省自然科学基金资助项目(NoY207432)

摘　　要：目的探讨二氢青蒿素联合环氧化酶2抑制剂对S180肉瘤的生长抑制作用及其可能的机制。方法采用ICR小鼠皮下移植瘤模型,观察二氢青蒿素联合环氧化酶2抑制剂对小鼠S180肉瘤生长抑制作用,以及对肿瘤COX-2、VEGF、CD31蛋白表达与白细胞数目的影响。结果二氢青蒿素分别以50、100、150mg·kg-1剂量与环氧化酶2抑制剂美洛昔康10mg·kg-1剂量合用能明显抑制S180肉瘤的生长,抑瘤率最高达55.38%,优于两药单用的效果;免疫组织化学检测表明,3个剂量的二氢青蒿素合用环氧化酶2抑制剂的肿瘤组织COX-2、VEGF及CD31蛋白的表达量均下降;Westernblot方法检测得在高剂量二氢青蒿素(150mg.kg-1.d-1)联合应用美洛昔康(10mg.kg-1.d-1)组VEGF和COX-2蛋白的表达量均有下降,与模型对照组差异有显著性(P<0.05);RT-PCR检测得各合用药物组的肿瘤组织VEGFmRNA表达量均减少(P<0.05)。结论二氢青蒿素联合环氧化酶2抑制剂能明显抑制S180肉瘤的生长,其机制可能与下调肿瘤组织中COX-2和VEGF的表达有关。Aim To observe the inhibitory effect of dihydroartemisinin combined with COX-2 inhibitor on S180 sarcoma and their possible antitumor mechanisms. Methods The ICR mice model of the subcutaneous transplanting tumor was established by S180 sarcoma to investigate the treatment effect of dihydroartemisinin and COX-2 inhibitor. Expressions of VEGF, COX-2 and CD31 in S180 sarcoma were detected and the amount of leukocyte was also observed. Results Dihydroartemisinin combined with COX-2 inhibitor could potently inhibit tumor growth and inflammation. The maximal antitumor rate reached 55.38%. The results of immunohistochemistry showed that COX-2 and VEGF protein expressions were weakened by dihydro- artemisinin and COX-2 inhibitor, versus the control groups. Further, RT-PCR analysis showed that the expression of VEGF mRNA was also effectively decreased. Finally, a significant down-regulation effect of COX-2 and VEGF protein expression was observed. Conclusions Dihydroartemisinin combined with COX-2 inhibitor can significantly inhibit S180 tumor. The antitumor mechanism of these two drugs might be closely related to the effect of COX-2 and VEGF expression suppression.

关 键 词：二氢青蒿素 环氧化酶2抑制剂 血管内皮生长因子 S180肉瘤 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]