Shapira A, Virolainen E, Jameson J J, Ossakow S J, Carey T E
Arch Otolaryngol Head Neck Surg. 1986 Nov;112(11):1151-8. doi: 10.1001/archotol.1986.03780110027002.
Six laryngeal squamous cell carcinoma (SCC) cell lines and the MCF-7 breast cancer line, all of which contain estrogen and progesterone receptors, were tested for in vitro growth inhibition by the antiestrogen tamoxifen citrate. Cell line MCF-7 was more sensitive to growth retardation at 1 mumol/L of tamoxifen citrate, but SCC lines showed higher sensitivity than MCF-7 to cytotoxic effects at higher drug concentrations (7 to 10 mumol/L). A cytostatic level of growth inhibition was produced by 5 mumol/L tamoxifen citrate for both types of cell lines. When tamoxifen and estradiol were added to cultures simultaneously, partial reversal of growth inhibition was observed with MCF-7 but not with UM-SCC-5. All of the cell lines recovered from inhibition when tamoxifen was replaced with 0.1 mumol/L estradiol, but laryngeal SCC lines recovered equally well in estradiol-free medium, whereas MCF-7 recovered only partially in the absence of estradiol. These findings indicate that there are at least two tamoxifen receptor sites--one for which estradiol is a competitor and one for which it is not--and that tamoxifen reversibly blocks growth and may synchronize SCC cells.
六种喉鳞状细胞癌(SCC)细胞系以及MCF-7乳腺癌细胞系(所有这些细胞系均含有雌激素和孕激素受体),接受了抗雌激素他莫昔芬柠檬酸盐的体外生长抑制测试。细胞系MCF-7在1 μmol/L他莫昔芬柠檬酸盐作用下对生长迟缓更敏感,但SCC细胞系在较高药物浓度(7至10 μmol/L)下对细胞毒性作用的敏感性高于MCF-7。5 μmol/L他莫昔芬柠檬酸盐对两种类型的细胞系均产生了生长抑制的细胞周期停滞水平。当同时将他莫昔芬和雌二醇添加到培养物中时,观察到MCF-7的生长抑制有部分逆转,但UM-SCC-5没有。当用0.1 μmol/L雌二醇替代他莫昔芬时,所有细胞系均从抑制中恢复,但喉SCC细胞系在无雌二醇培养基中恢复得同样好,而MCF-7在无雌二醇时仅部分恢复。这些发现表明,至少存在两个他莫昔芬受体位点——一个位点雌二醇是其竞争者,另一个位点则不是——并且他莫昔芬可逆地阻断生长并可能使SCC细胞同步化。