去氢表雄酮抗促癌作用及其机理  

STUDIES ON THE ANTI-TUMORPROMOTION ACTIVITIES OF DEHYDROEPIANDROSTERONE AND ITS MECHANISM OF ACTION

作　　者：杨笋[1] 付招娣[1] 韩锐[1] 

机构地区：[1]中国医学科学院,中国协和医科大学药物研究所,北京100050

出　　处：《药学学报》2001年第8期576-580,共5页Acta Pharmaceutica Sinica

摘　　要：目的　探讨去氢表雄酮 (dehydroepiandrosterone,DHEA)抗促癌作用及机理。方法　用激光聚焦显微镜、流式细胞术、免疫荧光染色及小鼠耳部急性炎症等方法。结果　DHEA可明显抑制促癌剂巴豆油引起的小鼠急性耳肿胀 ;DHEA对巴豆油诱发的表皮细胞ODC活性升高也有显著的抑制作用。 10 - 7mol·L- 1 DHEA预处理可阻断佛波酯(TPA)刺激引起的S期细胞增加 ,并且对 [Ca2 + ]i和pH升高均有明显抑制作用。此外DHEA预处理可有效抑制蛋白激酶C α(PKC α)的活化。结论　DHEA有明显的抗促癌活性 ,可能与其对ODC活性和Ca2 + PKCAIM To investigate the anti tumorpromoting activity of dehydroepiandrosterone (DHEA) and its mechanism of action. METHODS Using croton oil induced ear edema model and applying confocal laser scanning microscopy, flow cytometry, immuno fluorescent techniques to investigate the inhibitory effect of DHEA on tumor promotion. RESULTS DHEA 25 mg·kg -1 was shown to inhibit croton oil induced ear edema in mice by 51%. DHEA at dose of 40 mg·kg -1 and 10 mg·kg -1 exhibited inhibitory effects on croton oil induced ornithine decarboxylase (ODC) activity by 64% and 53%, respectively. These results revealed that DHEA can block the change of cell cycle and the percentage of S phase was decreased to 17% at concentration of 10 -7 mol·L -1 . The increase of [Ca 2+ ]i and pH as well as PKC activation induced by TPA stimulation were significantly inhibited by DHEA pretreatment. CONCLUSION The present experiments demonstrate that DHEA appears to be an attractive candidate as an anti tumorpromotion agent for tumor chemoprevention. The mechanism of its action might be related to its inhibitory effects on ODC activity and Ca 2+ DG PKC signal pathway.

关 键 词：去氢表雄酮 肿瘤化学预防作用 抗促癌作用 DHEA 药理学 

分 类 号：R965[医药卫生—药理学] R979.1[医药卫生—药学]