去氢表雄酮抗促癌作用及其机理

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⁺-PKC-DG信号传导通路的抑制有关

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

AIM: 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 ofCa2+]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.