Gottardis M M, Bischoff E D, Shirley M A, Wagoner M A, Lamph W W, Heyman R A
Department of Endocrine Research, Ligand Pharmaceuticals, Inc., San Diego, California 92121, USA.
Cancer Res. 1996 Dec 15;56(24):5566-70.
Recently, 9-cis retinoic acid, a high affinity ligand for retinoic acid receptors and retinoid X-receptors (RXRs), was shown to have efficacy superior to all-trans retinoic acid as a chemopreventive agent in the N-nitroso-N-methylurea-induced rat mammary carcinoma model. To further explore the specific contribution RXR activation may play in suppression of carcinogenesis, the efficacy of LGD1069 (Targretin), an RXR-selective ligand, in the N-nitroso-N-methylurea-induced rat mammary tumor model was studied. LGD1069-treated animals showed a 90% reduction in tumor burden and tumor incidence compared with vehicle-treated rats with an efficacy similar to that achieved with tamoxifen. LGD1069 was very well tolerated during 13 weeks of chronic therapy with no classic signs of "retinoid-associated" toxicities. These data demonstrate that LGD1069, an RXR-selective ligand, can act as a highly effective and benign chemopreventive agent for mammary carcinoma.
最近，9-顺式视黄酸作为视黄酸受体和类视黄醇X受体（RXRs）的高亲和力配体，在N-亚硝基-N-甲基脲诱导的大鼠乳腺癌模型中，被证明作为化学预防剂，其疗效优于全反式视黄酸。为了进一步探究RXR激活在抑制致癌作用中可能发挥的具体作用，研究了RXR选择性配体LGD1069（他扎罗汀）在N-亚硝基-N-甲基脲诱导的大鼠乳腺肿瘤模型中的疗效。与赋形剂处理的大鼠相比，接受LGD1069处理的动物的肿瘤负荷和肿瘤发生率降低了90%，其疗效与他莫昔芬相当。在13周的长期治疗中，LGD1069的耐受性良好，没有出现“类视黄醇相关”毒性的典型迹象。这些数据表明，RXR选择性配体LGD1069可作为一种高效且安全的乳腺癌化学预防剂。
