Ramu A, Glaubiger D, Fuks Z
Cancer Res. 1984 Oct;44(10):4392-5.
The effects of the triparanol analogues chlorotrianisene, clomiphene, tamoxifen, 5-[p-(fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol (MDL 10393), MDL 8917v, nafoxidine, 2-[p-(6-methoxy-2-phenylinden-3-yl)phenoxy]triethylamine (U-11555A), 2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]triethylamine (U-10520A), and nitromifene, as well as triparanol itself, were studied in the P388 murine leukemia cell line and in a doxorubicin-resistant subline (P388/ADR). At noninhibitory concentrations, all the analogues increased the sensitivity of P388/ADR cells to doxorubicin but did not have such an effect on the doxorubicin-sensitive cells. Diethylstilbestrol, deacetylated cyclofenil (F6060), hexestrol, and 17 beta-estradiol did not have such an activity. The effects of tamoxifen on doxorubicin sensitivity of P388/ADR cells could not be reversed by 17 beta-estradiol. Estrogen receptors could not be demonstrated in either cell line. It is therefore suggested that the reversal of the doxorubicin-acquired resistance by the triparanol analogues is unrelated to their estrogenic or antiestrogenic activities. The possible clinical implications of these findings are discussed.
在P388小鼠白血病细胞系和阿霉素耐药亚系（P388/ADR）中研究了三苯乙醇类似物氯烯雌醚、氯米芬、他莫昔芬、5-[对-(芴-9-亚甲基)苯基]-2-哌啶乙醇（MDL 10393）、MDL 8917v、奈福昔定、2-[对-(6-甲氧基-2-苯基茚-3-基)苯氧基]三乙胺（U-11555A）、2-[对-(3,4-二氢-6-甲氧基-2-苯基-1-萘基)苯氧基]三乙胺（U-10520A）、硝米芬以及三苯乙醇本身的作用。在非抑制浓度下，所有类似物均增加了P388/ADR细胞对阿霉素的敏感性，但对阿霉素敏感细胞没有这种作用。己烯雌酚、去乙酰环芬尼（F6060）、己烷雌酚和17β-雌二醇没有这种活性。17β-雌二醇不能逆转他莫昔芬对P388/ADR细胞阿霉素敏感性的影响。在这两种细胞系中均未检测到雌激素受体。因此提示，三苯乙醇类似物对阿霉素获得性耐药的逆转与其雌激素或抗雌激素活性无关。讨论了这些发现可能的临床意义。
