新型孕激素受体阻断剂ZXH951对小鼠激素依赖性乳腺癌MXT的抑制作用

Antitumor effect of ZXH951,a novel progesterone receptor antagonist,on hormone dependent mouse MXT mammary transplantable tumor

目的 :研究新型孕激素受体阻断剂ZXH95 1的体内抗肿瘤作用及联合用药的增效作用。为临床激素依赖性乳腺癌的内分泌治疗提供理论及实验依据。方法 :采用小鼠移植性MXT激素依赖性乳腺肿瘤模型 ,观察了ZXH95 1对MXT的抑制作用 ,并进一步观察了ZXH95 1与他莫西芬联合用药对MXT的抑制作用。结果 :ZXH95 1在 12 .5 ,2 5 ,5 0mg·kg-1剂量下 ,对小鼠乳腺癌MXT有显著抑制作用 ,肿瘤抑制率分别为 (71.3± 8.0 8) % ,(88.0±2 .6 5 ) % ,(89.7± 2 .5 2 ) %。采用更小剂量 6 .2 5mg·kg-1与他莫西芬 4.0mg·kg-1联合用药 ,抑制率达 94%。结论 :ZXH95 1对小鼠移植性MXT激素依赖性乳腺肿瘤有较强的治疗作用 ,与抗雌激素药他莫西芬合用 ,疗效更好。提示ZXH95 1是一个有发展前景的新型的乳腺癌内分泌治疗药物。

Objective:To study the in vivo antitumor effe ct of ZXH951, a novel progesterone receptor antagonist, and its efficacy enhanceme nt after combination administration with tamoxifen.Methods:The transplantable mouse hormone dependent MXT mammary tu mor model was adopted for observating the antitumor effects of ZXH951.The effect s of ZXH951 in combination therapy with tamoxifen was also observed.Results:At the dosage of 12.5,25,50 mg·kg -1 ,ZXH951 signifi cantly inhibited the growth of mouse MXT mammary transplantable tumor, and the i nhibitory percent was 71.3± 8.08,88.0±2.65 and 89.7±2.52 respectively.ZXH9 51 6.25 mg·kg -1 in combined with tamoxifen 4.0 mg·kg -1 exhibited a sy nergistic inhibitory effect and the inhibitory was above 94%.Conclusion:ZXH951 is a good candidate of new drugs for endocrine therapy of breast cancer.