Dihydrotestosterone (DHT) modulates the ability of NSAIDs to induce apoptosis of prostate cancer cells.
Dihydrotestosterone (DHT) modulates the ability of NSAIDs to induce apoptosis of prostate cancer cells.
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二氢睾酮 (DHT) 调节 NSAID 诱导前列腺癌细胞凋亡的能力。
DOI：
10.1007/s00280-001-0384-4
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Djakiew,Daniel
中科院分区：
文献类型：
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作者：
Andrews,Peter;Krygier,Scott;Djakiew,Daniel
目的：最近的证据表明，非类固醇抗炎药(NSAIDs)在前列腺癌的治疗和预防中是有效的。本研究旨在探讨类固醇激素双氢睾酮(DHT)对非甾体抗炎药非甾体抗炎药(NSAID)诱导前列腺癌细胞凋亡的调节作用。材料与方法：采用体外培养的雄激素敏感和雄激素不敏感的人前列腺癌细胞模型，观察不同浓度DHT作用下，特异性环氧合酶-2抑制剂(NS-398)和非特异性环氧合酶抑制剂(吲哚美辛)诱导细胞凋亡的作用。结果：随着双羟色胺浓度的增加，NS-398和消炎痛诱导雄激素敏感的LNCaP细胞凋亡的能力明显增强。然而，NSAIDs诱导雄激素不敏感的PC-3细胞凋亡的能力不受DHT的存在的影响。在NSAIDs作用前后，孵育液中较高水平的DHT促进了LNCaP细胞的凋亡。另一种与LNCaP细胞中的雄激素受体相互作用的类固醇激素(孕酮)也促进了这些细胞的凋亡。随着DHT浓度的增加，LNCaP细胞从S期和G2/M期进入G0/G1期。结论：DHT联合NSAIDs治疗前列腺癌是一项重要的临床试验，因为雄激素治疗前列腺癌是一种常见的治疗方法。
Purpose:Recent evidence indicates that nonsteroidal antiinflammatory drugs (NSAIDs) are effective in the treatment and prevention of prostate cancer. In the study reported here, we investigated the ability of the steroid hormone dihydrotestosterone (DHT) to modulate NSAID-induced apoptosis of prostate cancer cells.Materials and methods:Using in vitro models of androgen-sensitive and androgen-insensitive human prostate cancer cells, we evaluated the ability of a specific cyclooxygenase-2 inhibitor (NS-398) and a nonspecific cyclooxygenase inhibitor (indomethacin) to induce apoptosis in the presence of various concentrations of DHT. Apoptosis was quantified using the TUNEL method and verified by electron microscopy.Results:We found that increasing concentrations of DHT significantly enhanced the ability of NS-398 and indomethacin to induce apoptosis of androgen-sensitive LNCaP cells. The ability of NSAIDs to induce apoptosis of androgen-insensitive PC-3 cells, however, was not affected by the presence of DHT. Higher levels of DHT in the incubation medium both before as well as following exposure to NSAIDs enhanced apoptosis of LNCaP cells. Another steroid hormone that interacts with the androgen receptor in LNCaP cells (progesterone) also promoted apoptosis of these cells. Increasing concentrations of DHT caused LNCaP cells to shift from the S and G2/M to the G0/G1stages of the cell cycle.Conclusions:These observations support the use of DHT in combination with NSAIDs in the treatment of prostate cancer, and indicate that DHT is an important issue to address in clinical trials of NSAIDs since androgen ablation is a common treatment for prostate cancer.