Mohammed M Q, Photiou A, Shah P, Retsas S
Catherine Griffiths Cancer Research Laboratory, Department of Medical Oncology, Charing Cross Hospital, London, UK.
Anticancer Res. 1995 Jul-Aug;15(4):1319-26.
Cisplatin and carboplatin have been used against human malignant melanoma as single agents and in combination. Tamoxifen is used in the treatment of breast cancer, but has no significant activity against human malignant melanoma. Tamoxifen, however, has been promoted as a modulator in some drug regimens. The addition of tamoxifen to cisplatin or carboplatin has been reported to enhance their activity against the human melanoma cell line T-289. We investigated whether tamoxifen potentiates, in vitro, the activity of cisplatin and carboplatin against C32, G361 and StMl11a melanoma cell lines. Tamoxifen alone at clinically achievable concentrations of 0.1 and 1.0 microM (168 hrs exposure) had no significant effect on growth. No chemopotentiation of the activity of cisplatin or carboplatin was observed with the addition of tamoxifen (0.1 and 1.0 microM). The platinum drugs were added for 1 hr (serially diluted from 100.0 microM). Against the G361 line there was a trend towards chemopotentiation of cisplatin by 0.1 microM of tamoxifen. However, this did not reach statistical significance. Tamoxifen (5.0 and 10.0 microM) produced some inhibitory activity, and a trend towards synergy with cisplatin was observed. However, these concentrations are not clinically feasible. Previous reports detecting synergistic interaction between tamoxifen (0.1 and 1.0 microM), and the platinum compounds against the T-289 melanoma cell line cannot be supported in our in vitro system.
顺铂和卡铂已被单独或联合用于治疗人类恶性黑色素瘤。他莫昔芬用于治疗乳腺癌,但对人类恶性黑色素瘤没有显著活性。然而,他莫昔芬在一些药物治疗方案中被用作调节剂。据报道,在顺铂或卡铂中添加他莫昔芬可增强它们对人黑色素瘤细胞系T - 289的活性。我们研究了他莫昔芬在体外是否能增强顺铂和卡铂对C32、G361和StMl11a黑色素瘤细胞系的活性。单独使用他莫昔芬,在临床可达到的浓度0.1和1.0微摩尔/升(暴露168小时)时对细胞生长没有显著影响。添加他莫昔芬(0.1和1.0微摩尔/升)后,未观察到顺铂或卡铂活性的化学增敏作用。铂类药物添加1小时(从100.0微摩尔/升连续稀释)。对于G361细胞系,0.1微摩尔/升的他莫昔芬有使顺铂化学增敏的趋势。然而,这未达到统计学显著性。他莫昔芬(5.0和10.0微摩尔/升)产生了一些抑制活性,并且观察到与顺铂有协同作用的趋势。然而,这些浓度在临床上不可行。之前关于他莫昔芬(0.1和1.0微摩尔/升)与铂类化合物对T - 289黑色素瘤细胞系存在协同相互作用的报道在我们的体外系统中未得到证实。