探討薑黃素在攝護腺癌細胞移動、侵襲及間質蛋白酶活化之抑制效用

Abstract

在美國，攝護腺癌是男性常見癌症之一。在台灣，攝護腺癌的發生率有逐年上升現象，且在2008年行政院衛生署癌症發生統計中，排名第七。隨著攝護腺癌病期演進，癌細胞常惡性轉移至淋巴結或骨頭，造成癌症治療困難。近來研究指出鬱金粉中的主要成分薑黃素 (Curcumin)，具有對抑制攝護腺癌病情演進的化學預防能力。然而薑黃素如何去抑制癌細胞侵襲的機轉目前尚未完全了解。從目前的研究中我們測試了薑黃素對人類攝護腺癌細胞株PC-3 的細胞毒性、增生、移動力，以及侵襲能力的影響。我們的結果顯示，薑黃素可以顯著地抑制細胞的增生、移動和侵襲能力。另外，薑黃素也參與了抑制第二型穿膜絲胺酸蛋白酶─間質蛋白酶 (Matriptase)的活化。在許多癌症中包括攝護腺癌，不正常活化的基質蛋白酶被認為參與促進癌症病情演進。為了更進一步探討薑黃素對於基質蛋白酶抑制的效果，從即時聚合酶連鎖反應和免疫點墨法分析的結果，得知薑黃素並不影響基質蛋白酶的基因表現量，但是會促進已活化的膜上基質蛋白酶脫落至膜外環境。此外，藉由評估基質蛋白酶的受質─Prostasin的量，發現薑黃素可以顯著地抑制基質蛋白酶的活性。綜合以上，從我們的結果得知薑黃素具有藉由壓抑基質蛋白酶活化及活性的效果，達到抑制攝護腺癌病情演進的潛力。

Prostate adenocarcinoma is one of the most common cancer among men in USA. In Taiwan, the incidence of prostate cancer is steadily rising and the seventh cancer lesion since 2008. During the prostate cancer progression, cancer cells often metastasize to lymph nodes or bone, leading to poor prognosis. Recent studies have shown that curcumin (diferuloylmethane), a major chemical component of turmeric, has been shown to possess a cancer chemopreventive potential against prostate cancer. However, the mechanism of curcumin that suppress the invasion of prostate cancer cells is not fully understood. In the current study, we examined the effect of curcumin on cell cytotoxitcy, proliferation, migration and invasion in a human prostate cancer cell line, PC-3. Our results showed that curcumin could significantly suppress prostate cancer cell proliferation, migration and invasion. Moreover, curcumin was also involved in inhibiting activation of matriptase, which is a type II transmembrane serine protease. Deregulated matriptase activation has been proposed to promote the progression of many cancers including prostate cancer. To further investigate the inhibitory effect of curcumin on matriptase activation, the results of real-time PCR and immunoblot analysis indicated that curcumin treatments did not affect gene expression of matriptase but did promote activated matriptase shedding into extracellular environment. In addition, curcumin showed a significant reduction in matriptase activity by evaluating the status of prostatsin, which is a known substrate of matriptase. In summary, our results suggested that curcumin potentiates an anti-progression effects on prostate cancer at least in part by suppressing matriptase function.