丹參酮IIA 藉由阻斷雄性素受體的轉錄活性而抑制LNCaP 細胞的生長

Tanshinone IIA Inhibits the Growth of LNCaP Cells by Blocking the Transcriptional Activity of Androgen Receptor

雄性素受體（Androgen receptor, AR）是激素受體家族的一種核轉錄因子。在雄性素受體依賴性前列腺癌（AR-dependent prostate cancer） 中，雄性素受體對於前列腺癌的發生與進展扮演著重要的角色。我們的研究發現，0.1 μM 的tanshinone IIA 即能抑制雄性素受體下游蛋白的 mRNA 和蛋白質表現的水平，顯示tanshinone IIA 在低濃度即能阻斷活化的雄性素受體的轉錄活性。此外，我們亦發現，tanshinone IIA 能抑制雄性素受體的穩定性，但不影響雄性素受體的 mRNA 水平。同時我們發現，丹參酮IIA（tanshinone IIA）能抑制雄性素受體依賴性前列腺癌細胞株LNCaP 細胞的生長。此抑制作用在加入雙氫睾酮（dihydrotestosterone，DHT）活化之LNCaP 細胞表現的較沒有加入DHT 之LNCaP 細胞更為明顯，表示tanshinone IIA 可能透過影響雄性素受體的功能來抑制LNCaP 細胞的生長。綜合上述，我們發現tanshinone IIA 在低濃度能有效的抑制雄性素受體的活化、阻斷雄性素受體目標基因（target gene）的表現，進而抑制前列腺癌細胞株LNCaP 細胞的生長。我們的研究認為，tanshinone IIA 有潛力成為治療前列腺癌的藥物。 Androgen receptor (AR) is a nuclear transcription factor of the hormone receptor family. For some prostate cancers, named AR-dependent prostate cancer, it plays an important role for the development and progress of prostate cancer. In this study, we showed 0.1μM tanshinone IIA can inhibit the expression of mRNA and protein level in AR downstream proteins. It suggests tanshinone IIA can block the transcriptional activity of activated ARs by lower concentration. We also showed tanshinone IIA can suppress stability of AR protein, but not the mRNA level of AR. We also found tanshinone IIA can inhibit the growth of LNCaP cells, AR-dependent prostate cancer cell line. This inhibitory effect is stronger on LNCaP cells stimulated by dihydrotestosterone (DHT) than without DHT, suggesting that tanshinone IIA can inhibit the growth of LNCaP cells through affecting the function of AR. In summary, we discovered tanshinone IIA can efficiently inhibit AR transactivation, block AR target genes expression in low concentration (0.1 μM), and then inhibit cell growth in AR positive LNCaP cells. Our results suggest that tanshinone IIA could be a potential agent for the treatment of prostate cancers.