Davidson N E, Mank A R, Prestigiacomo L J, Bergeron R J, Casero R A
Johns Hopkins Oncology Center, Baltimore, Maryland 21231.
Cancer Res. 1993 May 1;53(9):2071-5.
Previous studies have documented differential sensitivity of human lung cancer and melanoma cell lines to the cytotoxic effects of N1, N12-bis(ethyl)spermine (BESpm). We show here that BESpm can significantly inhibit the growth of six human breast cancer cell lines with 50% inhibitory concentration in the microM range. The degree of inhibition does not correlate with estrogen receptor status. Detailed studies with estrogen receptor-positive MCF-7 and estrogen receptor- negative Hs578t cells show a similar dose-response curve with concentrations of 1-10 microM resulting in maximal growth inhibition. Growth inhibition in both lines is associated with an 8-12-fold induction of the polyamine catabolic enzyme, spermidine/spermine N1-acetyltransferase, and a progressive decrease in intracellular polyamine levels over 6 days even though steady-state levels of BESpm are achieved within 24 h. Similar studies on WTMCF7 and AdrRMCF7 cells show that the acquisition of resistance to hormonal or doxorubicin therapy is not associated with resistance to the growth-inhibitory effects of BESpm. These results suggest that BESpm exerts similar growth-inhibitory effects against both hormone-responsive and -unresponsive human breast cancer cells, a finding which has significance for the potential use of polyamine analogues in treating human breast cancer.
先前的研究已经证明人类肺癌和黑色素瘤细胞系对N1,N12-双(乙基)精胺(BESpm)的细胞毒性作用存在差异敏感性。我们在此表明，BESpm能够显著抑制六种人类乳腺癌细胞系的生长，其50%抑制浓度在微摩尔范围内。抑制程度与雌激素受体状态无关。对雌激素受体阳性的MCF-7细胞和雌激素受体阴性的Hs578t细胞进行的详细研究显示，在1-10微摩尔的浓度下，二者具有相似的剂量反应曲线，均可导致最大程度的生长抑制。两株细胞系的生长抑制均与多胺分解代谢酶亚精胺/精胺N1-乙酰转移酶8至12倍的诱导以及细胞内多胺水平在6天内逐渐降低有关，尽管BESpm在24小时内达到稳态水平。对WTMCF7和AdrRMCF7细胞的类似研究表明，对激素或阿霉素治疗产生耐药性与对BESpm的生长抑制作用产生耐药性无关。这些结果表明，BESpm对激素反应性和无反应性的人类乳腺癌细胞均具有相似的生长抑制作用，这一发现对于多胺类似物在治疗人类乳腺癌中的潜在应用具有重要意义。
