摘要
维胺酸 (RⅡ )是中国医学科学院药物研究所研制的Ⅰ类新药。多中心临床观察证明 ,其对口腔白斑 ,胃和宫颈上皮不典型增生 ,外阴白色病损等癌前疾病具较好治疗作用。临床前研究证实维胺酸能明显抑制多种致癌物诱发的突变和减轻染色体损伤 ,可以阻遏TPA类物质对鸟氨酸脱羧酶 (ODC)活性的诱导 ,降低蛋白激酶C (PKC)活性 ,具有明显抗致突变、抗促癌作用。在一组由亚硝胺、DMBA诱发的动物口腔、胃、皮肤及膀胱癌及癌前病变的实验中 ,显示出它有明显抗化学致癌作用。RⅡ可以影响多种肿瘤细胞增殖 ,显示分化诱导作用。电镜组化、细胞周期分析等方法证实 ,药物作用后癌细胞在生物化学、形态、生长特性等方面恶性程度明显降低 ,细胞超微结构变化显著 ,向正常细胞方向分化。RⅡ对癌细胞运动、侵袭也显示一定的抑制作用。作用机理研究表明 ,RⅡ主要通过增强c fos基因表达 ,抑制c myc等基因表达 。
N 4 (carboxyphenyl)retinamide(RⅡ) is a new drug developed by the Institute of Materia Medica,Chinese Academy of Medical Sciences.The cancer chemopreventive action of RⅡ is reviewed in this paper.The multicenter clinical trials indicated that RⅡ was effective against premalignancies such as oral leukoplakia,vulvar leukoplakia,dysplasia of the uterine cervix and stomach.Preclinical studies demonstrated that RⅡ was a potent anti mutagenic and anti promotion agent.It has significant protective effects on chromosome aberration,and can inhibit ornithine decarboxyase (ODC) activity induced by 12 O tetradecanoylphorbol 3 acetate (TPA)and decreases protein kinase C (PKC)activity.In a panel of experimental models including DMBA induced buccal pouch carcinogenesis in hamster,DMBA and croton oil induced skin papilloma,nitrososamine induced forestomach carcinogenesis in mice,and N butyl N (4 hydroxybutyl) nitrosamine (BBN) induced bladder carcinogenesis in rats,it was demonstrated that RⅡ was a potent anti carcinogenic agent.Electron microscopic studies and cell cycle kinetic analysis revealed that RⅡ could decrease malignant degree of tumor cells in terms of cell morphology and growth characteristics,and tumor cells differentiation.Action mechanisms studies indicated that RⅡ inhibited the expression of oncogene c myc and enhanced the expression of c fos. In summary,RⅡ is a promising chemopreventive agent in terms of its anticarcinogenesis activity and clinical efficacy for the treatment of oral leukoplakia and vulvar leukoplakia. [
出处
《中国工程科学》
2000年第4期83-88,共6页
Strategic Study of CAE
基金
国家医药局"七五"攻关课题项目!(75-63-01-04)
