Maenpaa J, Wiebe V, Koester S, Wurz G, Emshoff V, Seymour R, Sipila P, DeGregorio M
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Cancer Chemother Pharmacol. 1993;32(5):396-8. doi: 10.1007/BF00735926.
An estrogen receptor-negative, multidrug-resistant MDA-MB-A1 human breast cancer cell line was grown in culture with and without a noninhibitory concentration (0.5 microM) of tamoxifen for 122 days. Tamoxifen-treated and control cells were inoculated into opposite flanks of nine nude mice, where they produced measurable tumors in every case. Six of the animals were treated with tamoxifen at 500 micrograms/day for 22 days. Although no inhibitory nor stimulatory effect of tamoxifen was seen in vitro, tamoxifen had a clear tumor-growth-stimulating effect in mice. The most pronounced stimulatory effects were observed in the cells that had been cultured with tamoxifen. Within 3 weeks of the start of tamoxifen therapy, the cells grown in the presence of tamoxifen produced tumors with a mean size of 380 mm2, whereas the cells not pretreated with tamoxifen had tumors of 220 mm2. In contrast, in mice not receiving tamoxifen, the sizes of the tumors were 190 and 140 mm2, respectively. These preliminary results suggest that prolonged in vitro tamoxifen exposure induces cellular changes that result in tumors that are stimulated to grow faster in mice following tamoxifen treatment.
一种雌激素受体阴性、多药耐药的MDA-MB-A1人乳腺癌细胞系在含有和不含有非抑制浓度（0.5微摩尔）他莫昔芬的培养基中培养122天。将经他莫昔芬处理的细胞和对照细胞接种到9只裸鼠的双侧胁腹，在每种情况下它们都产生了可测量的肿瘤。其中6只动物每天接受500微克他莫昔芬治疗22天。虽然在体外未观察到他莫昔芬的抑制或刺激作用，但他莫昔芬在小鼠中具有明显的肿瘤生长刺激作用。在用他莫昔芬培养的细胞中观察到最明显的刺激作用。在他莫昔芬治疗开始后的3周内，在他莫昔芬存在下生长的细胞产生的肿瘤平均大小为380平方毫米，而未用他莫昔芬预处理的细胞产生的肿瘤大小为220平方毫米。相比之下，在未接受他莫昔芬治疗的小鼠中，肿瘤大小分别为190和140平方毫米。这些初步结果表明，体外长期暴露于他莫昔芬会诱导细胞变化，导致肿瘤在接受他莫昔芬治疗后在小鼠中生长加快。
