de Cremoux P, Calvo F, Cost H, Gauville C, Lagier G, Abita J P, Lechat P
Laboratoire de Pharmacologie Oncologique, Université Paris VII, France.
Fundam Clin Pharmacol. 1987;1(5):347-55. doi: 10.1111/j.1472-8206.1987.tb00572.x.
The effect of 1,25-dihydroxycholecalciferol [1,25(OH)2D3], the active form of vitamin D3, on cell growth, clonogenicity, and cyclic adenosine monophosphate (cAMP) production was examined in human breast cancer cell line T47D. 1,25(OH)2D3 markedly inhibited proliferation of T47D cells in a time- and concentration-dependent manner. 1,25(OH)2D3 5 X 10(-7) reduced to 70% [3H]thymidine incorporation into DNA. Specific high affinity nuclear receptors for 1,25(OH)2D3 were present in this cell line. The cAMP produced by T47D cells was measured during 10 min stimulation by effectors (prostaglandin E1 or forskolin). Without effector, T47D cells produced similar amounts of cAMP in control and 1,25(OH)2D3-treated cells. After 3 days in the presence of 1,25(OH)2D3, cAMP production was significantly increased compared to control cells when stimulated by 10(-4) M prostaglandin E1 or 5 X 10(-7) M forskolin (3.2- and 2.4-fold increase, respectively). This cAMP increase was concentration dependent within the same range that inhibited cell growth and clonogenicity. These results suggest that 1,25(OH)2D3 may indirectly affect cAMP production by modulating the target cell response to stimulatory agents of cAMP production.
在人乳腺癌细胞系T47D中检测了维生素D3的活性形式1,25 - 二羟胆钙化醇[1,25(OH)2D3]对细胞生长、克隆形成能力和环磷酸腺苷(cAMP)产生的影响。1,25(OH)2D3以时间和浓度依赖性方式显著抑制T47D细胞的增殖。1,25(OH)2D3浓度为5×10(-7)时，[3H]胸苷掺入DNA的量减少至70%。该细胞系中存在1,25(OH)2D3特异性高亲和力核受体。在效应物(前列腺素E1或福斯高林)刺激10分钟期间，测定T47D细胞产生的cAMP。在没有效应物的情况下，T47D细胞在对照细胞和1,25(OH)2D3处理的细胞中产生相似量的cAMP。在存在1,25(OH)2D3的情况下培养3天后，当用10(-4)M前列腺素E1或5×10(-7)M福斯高林刺激时，与对照细胞相比，cAMP的产生显著增加(分别增加3.2倍和2.4倍)。这种cAMP的增加在抑制细胞生长和克隆形成能力的相同范围内呈浓度依赖性。这些结果表明，1,25(OH)2D3可能通过调节靶细胞对cAMP产生刺激剂的反应来间接影响cAMP的产生。
