白藜芦醇对癌的化学预防作用  

Chemopreventive Effect of Resveratrol to Cancer

作　　者：付招娣[1] 曹玉[1] 王凯风[1] 徐少锋[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：《癌症》2004年第8期869-873,共5页Chinese Journal of Cancer

摘　　要：背景与目的白藜芦醇广泛存在于药食两用植物中,其开发利用已得到越来越多的关注。本研究旨在依据癌发生、发展的多阶段理论,选用经典的动物模型,从多个靶点探讨白藜芦醇对癌的化学预防作用。方法采用抗Ames法、抗微核法检测白藜芦醇抗突变作用。巴豆油诱发的小鼠耳肿胀和小鼠表皮组织中鸟氨酸脱羧酶的活性来判断其抗促癌作用。通过检测二甲基苯蒽/巴豆油诱发的小鼠皮肤二阶段乳头状瘤模型全面观察其对肿瘤发生的抑制作用。结果白藜芦醇可以明显减少致癌剂诱发的鼠伤寒沙门氏菌TA100回复突变菌落数,每皿用量100μg对甲基磺酸甲酯作用的抑制率达42.2%,每皿200μg对苯并芘作用的抑制率达91.8%。提前灌喂白藜芦醇可以显著对抗环磷酰胺诱发的小鼠骨髓嗜多染红细胞微核增加,并呈现较好的剂量依赖关系。将白藜芦醇以每日30mg/kg剂量灌喂6天,能有效减轻致炎剂引起的小鼠耳部急性炎性反应。以每日180mg/kg剂量给药3天,对巴豆油激发的小鼠表皮组织鸟氨酸脱羧酶活性增高抑制率达69.3%。应用白藜芦醇可以推迟二甲基苯蒽/巴豆油诱发的小鼠皮肤乳头状瘤发生时间,降低肿瘤发生率,减少平均荷瘤数。结论白藜芦醇在癌发生的突变、促癌及演进各阶段均可发挥积极的对抗作用。作为癌化学预防剂,具有较好的开发应用前景。BACKGROUND &OBJECTIVE: Carcinogenesis is a complex process and at least 3 stages, including initiation, promotion, and progression, have been proposed in the process of carcinogenesis. Resveratrol has attracted considerable attention due to its low toxicity and unique chemical structure. This study was designed to test chemopreventive effect of resveratrol to cancer using various animal models. METHODS:Ames assay and micronucleus formation assay were used to test the antimutagenic activities of resveratrol. Croton oil induced enhancement of ornithine decarboxylase (ODC) activities of dorsal epidermis cells in mouse and mouse ear edema model were used to investigate the anti promotion effect of resveratrol. In addition,7,12 dimenthylbenzanthracene (DMBA)/croton oil induced mouse skin tumor model was used to evaluate chemopreventive effect of resveratrol to cancer in vivo. RESULTS: In Ames test,100 μg/plate of resveratrol exhibited 42.2%of inhibition on the reversion of Salmonella typhimurium TA100 induced by methylmethansulfonate, and 200 μg/plate of resveratrol exhibited 91.8%of inhibition on the reversion induced by benzopyrene.Pretreatment of resveratrol prevented cyclophosphamide (CTX) induced micronucleus formation of polychromatic erythrocytes of mice bone marrow in dose dependent manner. Mice treated with 30 mg/kg of resveratrol for 6 days before croton oil exposure have palliative ear edema. Treatment of 180 mg/kg resveratrol for 3 days caused 69.3%decrease of ODC activities in croton oil induced dorsal epidermis. It was shown that resveratrol could inhibit DMBA/croton oil induced mouse skin papilloma, which includes prolonging the latent period of tumor occurrence, decreasing the incidence of papilloma, and reducing tumor number per mouse in dose dependent manner. CONCLUSION: Resveratrol has the ability of anti mutation and anti promotion of cancer and merit further studies as a potential cancer chemopreventive agent.

关 键 词：白藜芦醇 癌化学预防 抗始发突变 抗促癌 

分 类 号：R730.1[医药卫生—肿瘤]