Foury O, Nicolas B, Joly-Pharaboz M O, André J
INSERM-U 329, Hôpital Debrousse, Lyon, France.
J Steroid Biochem Mol Biol. 1998 Aug;66(4):235-40. doi: 10.1016/s0960-0760(98)00038-7.
The responses, in terms of cell proliferation and c-myc messenger RNA content, of human prostate cancer cells to androgen-receptor ligands were investigated. Experiments were performed with three types of cells (LNCaP, R2 and MOP) and three compounds (the androgen R 1881 and two anti-androgens: cyproterone acetate, CYPA, and RU 56187). MOP cells were established in the laboratory and the effects of RU 56187 had not been studied in culture. In terms of proliferation, LNCaP was stimulated by the three compounds, R2 was inhibited by R 1881 and RU 56187 but was stimulated by CYPA while MOP was inhibited by the three compounds. In the three types of cells, c-myc messenger RNAs were down regulated by R 1881 and RU 56187 but not by CYPA. The conclusions are: (1) the sets of responses of cell proliferation to three androgen-receptor ligands are cell specific; (2) the control of c-myc messenger RNA by R 1881 and RU 56187 may be related to the inhibition of cell proliferation by these compounds but not to their stimulatory effect on cell proliferation; (3) if prostate tumor cells would respond in vivo to androgens and antiandrogens like in culture, patients with prostate cancer could take benefits of reversible medical castration and sequential prescription of various antiandrogens.
研究了人前列腺癌细胞对雄激素受体配体的细胞增殖反应及c-myc信使核糖核酸含量。实验使用了三种细胞(LNCaP、R2和MOP)和三种化合物(雄激素R 1881以及两种抗雄激素药物:醋酸环丙孕酮,CYPA,和RU 56187)。MOP细胞是在实验室建立的,且尚未在培养中研究过RU 56187的作用。在增殖方面,三种化合物均刺激LNCaP细胞,R2细胞被R 1881和RU 56187抑制,但被CYPA刺激,而MOP细胞则被这三种化合物抑制。在这三种类型的细胞中,R 1881和RU 56187下调c-myc信使核糖核酸,但CYPA没有。结论如下:(1)三种雄激素受体配体对细胞增殖的反应模式具有细胞特异性;(2)R 1881和RU 56187对c-myc信使核糖核酸的调控可能与这些化合物对细胞增殖的抑制作用有关,而与其对细胞增殖的刺激作用无关;(3)如果前列腺肿瘤细胞在体内对雄激素和抗雄激素的反应与在培养中一样,前列腺癌患者可能会从可逆性药物去势及序贯使用各种抗雄激素药物中获益。