Fong C J, Sutkowski D M, Braun E J, Bauer K D, Sherwood E R, Lee C, Kozlowski J M
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611.
J Urol. 1993 May;149(5):1190-4. doi: 10.1016/s0022-5347(17)36345-0.
We studied the effect of retinoic acid on the growth and secretory activity of the androgen-responsive prostatic carcinoma cell line LNCaP. Our data showed that retinoic acid at 0.01 microM. stimulated the proliferation of LNCaP cells but inhibited their growth at 0.1 microM. under androgen-free conditions. In the presence of 0.1 nM. dihydrotestosterone (DHT), LNCaP cell proliferation was inhibited by 10 microM. retinoic acid but not by lower concentrations of retinoic acid. Retinoic acid reduced LNCaP cell growth at concentrations of 0.1 microM. in the presence of 10 nM. DHT. Retinoic acid (10 microM.) also reduced the growth response of LNCaP cells to epidermal growth factor and transforming growth factor alpha and potentiated the inhibitory effect of transforming growth factor beta. In additional studies, retinoic acid induced a dose-dependent increase in prostate specific antigen (PSA) secretion at concentrations of 0.1 to 1 microM. Dihydrotestosterone (10 nM.) also enhanced the secretion of PSA by LNCaP cells, and this effect was potentiated in a dose-dependent fashion by the addition of retinoic acid at 0.1-10 microM. Competitive binding studies showed that retinoic acid did not bind to androgen receptors. Overall, retinoic acid had a biphasic effect on LNCaP proliferation and promoted the secretion of PSA. The biphasic effect of retinoic acid on LNCaP growth should be considered in designing in vivo studies to determine the impact of retinoic acid on solid prostatic tumor growth. In addition, the ability of retinoic acid to increase PSA secretion may complicate the interpretation of serum PSA levels used for diagnostic and prognostic purposes.
我们研究了视黄酸对雄激素反应性前列腺癌细胞系LNCaP生长和分泌活性的影响。我们的数据显示，在无雄激素条件下，0.01微摩尔的视黄酸刺激LNCaP细胞增殖，但0.1微摩尔时抑制其生长。在存在0.1纳摩尔二氢睾酮（DHT）的情况下，10微摩尔视黄酸抑制LNCaP细胞增殖，而较低浓度的视黄酸则无此作用。在存在10纳摩尔DHT时，0.1微摩尔的视黄酸降低LNCaP细胞生长。10微摩尔视黄酸还降低LNCaP细胞对表皮生长因子和转化生长因子α的生长反应，并增强转化生长因子β的抑制作用。在其他研究中，视黄酸在浓度为0.1至1微摩尔时诱导前列腺特异性抗原（PSA）分泌呈剂量依赖性增加。10纳摩尔二氢睾酮也增强LNCaP细胞的PSA分泌，并且在加入0.1 - 10微摩尔视黄酸时，这种作用呈剂量依赖性增强。竞争性结合研究表明视黄酸不与雄激素受体结合。总体而言，视黄酸对LNCaP增殖有双相作用并促进PSA分泌。在设计体内研究以确定视黄酸对实体前列腺肿瘤生长的影响时，应考虑视黄酸对LNCaP生长的双相作用。此外，视黄酸增加PSA分泌的能力可能会使用于诊断和预后目的的血清PSA水平的解释复杂化。
