Fioravanti L, Miodini P, Cappelletti V, DiFronzo G
Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Anticancer Res. 1998 May-Jun;18(3A):1703-8.
1,25-dihydroxycholecalciferol has been previously reported to negatively regulate human breast cancer cell growth.
The antiproliferative effect of 1,25-dihydroxycholecalciferol (Ro 21-5535) and of the two non hypercalcemic analogs (1a,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol+ ++, Ro 24-5531 and 1a,25-dihydroxy-16-ene-23-yne-26,27-hexafluoro-19-nor-cholec alciferol, Ro 25-6760) was studied in MCF-7 and MDAMB-468 human breast cancer cell lines. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Steroid receptor modulation was investigated by radioligand assay.
The most effective drug was the Ro 25-6760 which at concentrations ranging between 1-100 nM caused a dose dependent growth inhibition apparently due to accumulation in G0/G1. Vitamin D3 analogs (10 nM) significantly counteracted the growth stimulation induced by TGF-a and IGF-I as well as the paracrine stimulation observed in co-cultures. They antagonized estradiol-promoted growth stimulation and progestrone receptor induction in MCF-7 cells.
Vitamin D3 analogs represent a class of clinically attractive drugs for treatment of breast cancer due to their ability to counteract estradiol and growth factor-induced growth stimulation.
先前有报道称1,25 - 二羟基胆钙化醇对人乳腺癌细胞生长具有负调控作用。
研究了1,25 - 二羟基胆钙化醇（Ro 21 - 5535）以及两种非高钙血症类似物（1α,25 - 二羟基 - 16 - 烯 - 23 - 炔 - 26,27 - 六氟胆钙化醇，Ro 24 - 5531和1α,25 - 二羟基 - 16 - 烯 - 23 - 炔 - 26,27 - 六氟 - 19 - 去甲胆钙化醇，Ro 25 - 6760）对MCF - 7和MDAMB - 468人乳腺癌细胞系的抗增殖作用。通过流式细胞术评估细胞周期分布和细胞凋亡。通过放射性配体测定法研究类固醇受体调节。
最有效的药物是Ro 25 - 6760，其浓度在1 - 100 nM之间时会引起剂量依赖性生长抑制，这显然是由于在G0/G1期的积累所致。维生素D3类似物（10 nM）显著抵消了TGF - α和IGF - I诱导以及共培养中观察到的旁分泌刺激所引起的生长刺激。它们拮抗了MCF - 7细胞中雌二醇促进的生长刺激和孕酮受体诱导。
维生素D3类似物因其能够抵消雌二醇和生长因子诱导的生长刺激，代表了一类临床上有吸引力的乳腺癌治疗药物。
