A nonsteroidal anti-inflammatory drug, flufenamic acid, inhibits the expression of the androgen receptor in LNCaP cells.
A nonsteroidal anti-inflammatory drug, flufenamic acid, inhibits the expression of the androgen receptor in LNCaP cells.
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DOI：
10.1210/endo.140.11.7246
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发表时间：
1999-11
期刊：
影响因子：
4.8
通讯作者：
W. Zhu;A. Smith;C. Young
中科院分区：
文献类型：
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作者：
W. Zhu;A. Smith;C. Young
非甾体抗炎药（NSAIDs）通过抑制前列腺素的合成在结肠癌和其他疾病的化学预防中发挥着潜在的作用。在本报告中，我们利用雄激素应答的人前列腺癌细胞LNCaP细胞，研究了氟芬那酸（FA）和吡罗西康（PXM）两种非甾体抗炎药对雄激素刺激下癌细胞生长的影响。我们发现FA对LNCaP细胞的抑制作用明显高于PXM。FA显著降低雄激素诱导基因的表达，如前列腺特异性抗原（PSA）和同源结构域转录因子Nkx3.1，但PXM没有。体外转染实验表明，FA在转录水平下调PSA的表达。Western和northern blot分析表明，FA在mRNA和蛋白水平上抑制雄激素受体（AR）的表达。抑制AR表达可能是fa介导的雄激素诱导基因表达抑制的原因。我们的数据还显示，FA显著降低了AR启动子介导的转录活性。本研究提示AR可能是FA抑制LNCaP细胞生长的靶点。FA和其他类似的非甾体抗炎药可能是通过调节AR的表达来化学预防人类前列腺癌的潜在候选药物。
Nonsteroidal anti-inflammatory drugs (NSAIDs) play potential roles in chemoprevention of colon cancer and others by inhibiting prostaglandin synthesis. In this report, we used LNCaP cells, an androgen-responsive human prostate carcinoma cell line, to study the effects of two NSAIDs, flufenamic acid (FA) and piroxicam (PXM), on the cancer cell growth stimulated by androgens. We found that FA had much higher potency to inhibit LNCaP cell growth than PXM. FA dramatically reduced the expression of androgen inducible genes, such as prostate-specific antigen (PSA) and the homeo-domain transcription factor Nkx3.1, but PXM did not. In vitro transfection experiments showed that FA down regulated the PSA expression at the transcription level. Western and northern blot analyses demonstrated that FA inhibited the androgen receptor (AR) expression at mRNA and protein levels. Suppressed AR expression may be the cause of FA-mediated inhibition of the androgen inducible gene expression. Our data also showed that FA significantly reduced the AR promoter-mediated transcription activities. This study indicated that AR might be a target for FA to inhibit LNCaP cell growth. FA and other similar NSAIDs may be potential candidates for chemoprevention of human prostate cancer by modulating the expression of AR.