Koh J, Kubota T, Asanuma F, Yamada Y, Kawamura E, Hosoda Y, Hashimoto M, Yamamoto O, Sakai S, Maeda K
Department of Surgery, Social Insurance Saitama Chuo Hospital, Japan.
J Surg Oncol. 1992 Dec;51(4):254-8. doi: 10.1002/jso.2930510411.
The antitumor activity of a newly synthesized triphenylethylene derivative [(E)-4-[1-[4-[2-(dimethylamino)ethoxy-phenyl]-2-(4-isopropyl)phenyl-1- butenyl] phenyl monophosphate] (TAT-59) was investigated against human breast carcinoma xenografts in nude mice with reference to the changes of hormone receptors. Five strains (MCF-7, Br-10, R-27, ZR-75-1, and T-61) used for the experiments possessed cytosol estrogen receptor (ER), and their growth was estradiol dependent. Five mg of TAT-59 and tamoxifen citrate (TAM) per kg were administered p.o. daily except Sunday. TAT-59 showed a positive antitumor effect against MCF-7 and R-27, whereas TAM was effective on MCF-7, and their adverse effects detected by mortality rate, body weight loss, and spleen weight loss were similar to each other. The reduction of ER and production of progesterone receptor (PgR) after the treatment with TAT-59 were more potent than after TAM, suggesting that TAT-59 exerts its antitumor effect through binding to ER. These findings suggest that TAT-59 might merit use in clinical trials with breast cancers.
研究了一种新合成的三苯乙烯衍生物[（E）-4-[1-[4-[2-（二甲基氨基）乙氧基苯基]-2-（4-异丙基）苯基-1-丁烯基]苯基单磷酸酯]（TAT-59）对裸鼠人乳腺癌异种移植瘤的抗肿瘤活性，并参考了激素受体的变化。用于实验的五株细胞系（MCF-7、Br-10、R-27、ZR-75-1和T-61）均具有胞浆雌激素受体（ER），其生长依赖于雌二醇。除周日外，每天口服给予每千克5毫克的TAT-59和柠檬酸他莫昔芬（TAM）。TAT-59对MCF-7和R-27显示出阳性抗肿瘤作用，而TAM对MCF-7有效，通过死亡率、体重减轻和脾脏重量减轻检测到的它们的不良反应彼此相似。TAT-59治疗后ER的降低和孕激素受体（PgR）的产生比TAM治疗后更显著，表明TAT-59通过与ER结合发挥其抗肿瘤作用。这些发现表明TAT-59可能值得用于乳腺癌的临床试验。
