Moon R C, Mehta R G, Detrisac C J
Laboratory of Pathophysiology, IIT Research Institute, Chicago, IL 60616.
Cancer Detect Prev. 1992;16(1):73-9.
Although several retinoids have been evaluated for prevention of mammary carcinogenesis in rats and mice, retinyl acetate (RA) and N-(4-hydroxyphenyl)retinamide (4-HPR) proved most effective. In rats, dietary administration of the retinoids reduced the incidence and number, and increased the latency of N-methyl-N-nitrosourea (MNU)-induced mammary cancers. 4-HPR reduced the number of hyperplastic alveolar nodules (HAN) in MTV- mice and the number of tumors in MTV+ mice. Other studies indicate that the synergistic effect of retinoid administration and hormonal deprivation is more efficacious in prevention of MNU-induced mammary cancer than either modality alone. Furthermore, retinoids alone and the combination of retinoid and tamoxifen inhibit the appearance of mammary cancers following the surgical removal of the first cancer as well as inhibit the growth of established cancers. Again, the combined modality was the most effective. Retinoids also exert an antiproliferative effect upon the mammary epithelium in vivo, which is represented morphologically by a bare duct system with little branching, end buds, and few, if any, alveoli. In organ culture, retinoids inhibit mammary end bud differentiation and proliferation induced by insulin and prolactin or carcinogens.
尽管已经对几种类维生素A在大鼠和小鼠中预防乳腺癌发生的效果进行了评估，但结果显示醋酸视黄酯（RA）和N-(4-羟基苯基)视黄酰胺（4-HPR）最为有效。在大鼠中，通过饮食给予类维生素A可降低N-甲基-N-亚硝基脲（MNU）诱导的乳腺癌的发生率和数量，并延长其潜伏期。4-HPR减少了MTV-小鼠中增生性肺泡结节（HAN）的数量以及MTV+小鼠中的肿瘤数量。其他研究表明，给予类维生素A与激素剥夺的协同作用在预防MNU诱导的乳腺癌方面比单独使用任何一种方法都更有效。此外，单独使用类维生素A以及类维生素A与他莫昔芬的联合使用，在手术切除首例癌症后可抑制乳腺癌的出现，并抑制已形成癌症的生长。同样，联合治疗方法最为有效。类维生素A在体内对乳腺上皮也具有抗增殖作用，在形态学上表现为导管系统几乎没有分支、终末芽，且肺泡很少（如果有的话）。在器官培养中，类维生素A可抑制由胰岛素和催乳素或致癌物诱导的乳腺终末芽分化和增殖。
