托瑞米芬与醋酸甲孕酮(MPA)联合用药的体内外抗肿瘤作用

L. Kancas , M. Grönroos
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引用次数: 7

摘要

测定不同妇科肿瘤组织中雌激素(ER)和孕激素(PgR)受体水平。同样的肿瘤在体外暴露于托瑞米芬、MPA或它们的联合作用下,通过简单的生物发光法测量细胞内的三磷酸腺苷(ATP)来跟踪肿瘤的生长。共研究34例临床样本。用托瑞米芬、MPA及其联合治疗dmba诱导的乳腺肿瘤大鼠。大约一半的卵巢癌和6 / 7的子宫腺癌都含有雌激素受体。7例卵巢肿瘤中富含PgR的占25%,子宫腺癌占6例。与对照相比,托瑞米芬(浓度为1 μmol/l)可使9/34样品的活细胞数量减少50%以下,MPA(浓度为10 μmol/l)可使17/34样品的活细胞数量减少50%以下,联合用药可使25/34样品的活细胞数量减少50%以下。5例联合用药抗肿瘤效果为协同作用。在两个病例中,可以看到弱拮抗的迹象。在体内,托瑞米芬和MPA对dmba诱导的肿瘤具有明显的协同作用。效果是剂量依赖的,在足够高的剂量下,有可能根除肿瘤并治愈动物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antitumor effects of combination toremifene and medroxyprogesterone acetate (MPA) in vitro and in vivo

The estrogen (ER) and progesterone (PgR) receptor levels in various gynecological tumors were measured. The same tumors were exposed in vitro to toremifene, MPA or their combination and the growth of the tumors was followed by measuring the adenosine triphosphate (ATP) within the cells by a simple bioluminescence assay. Altogether 34 clinical samples were studied. DMBA-induced mammary tumors bearing rats were treated in vivo with toremifene, MPA and their combination.

About half of the ovarian cancers and 6 out of the 7 adenocarcinomas of uteri contained ER. The ovarian tumors were PgR rich in 25% and adenocarcinomas of uteri in 6 out of the 7 cases.

When compared to control toremifene (concentration 1 μmol/l) was able to decrease the number of living cells to 50% or less in 9/34 samples, MPA (concentration 10 μmol/l) in 17/34 samples, and the combination in 25/34 samples. In five cases the antitumor effect of the combination was synergistic. In two cases signs of weak antagonism were seen.

In vivo the antitumor effect of toremifene and MPA was clearly synergistic against DMBA-induced cancers. The effect was dose-dependent and at sufficiently high doses it was possible to eradicate the tumors and cure the animals.

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