| Summary: | 碩士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 98 === Prostate cancer is the second leading cause of cancer-related death in men of the western world. In Taiwan, the incidence and mortality of prostate cancer have been rising progressively in recent years. The high mortality of prostate cancer is mainly due to the cancer progression to an androgen-independent state and/or high cancer cell migration, invasion and metastasis. Curcumin, a polyphenol substance derived from the herbal remedy and dietary spice turmeric, has been shown with potent antioxidant, anti-inflammatory, anti-carcinogenic, and chemopreventive effects. However, the molecular mechanism how curcumin suppresses prostate cancer cell invasion is not well understood. In this study, I examined the effect of natural compound curcumin on cell proliferation, migration and invasion in human prostate cancer PC3 cells. The results showed that curcumin could significantly suppress prostate cancer cell proliferation, migration and invasion. To further investigate the molecular mechanism in which curcumin was able to inhibit prostate cancer cell migration and invasion, I examined the effect of curcumin on a tumor-promoting, membrane-anchored serine protease, matriptase, since recent studies have shown that dysregulation of matriptase activation can promote the progression of many cancers including prostate cancer. The data showed that curcumin was able to reduce the activated levels with no effect on its gene expression of matriptase. Moreover, the reduction of activated matriptase by curcumin was partly due to the curcumin promoting the shedding of activated matriptase into extracellular environment. Furthermore, we established a PC-3 cell invasion progression model (parental and M2I1 PC-3 cells) with an increasing cell invasion capability and examined the effect of curcumin on different PC-3 cell invasion. The invasive ability of M2I1 cells was enhanced by approximate one fold, compared to the parental PC-3 cells. Curcumin-decreased M2I1 cell invasion was partly due to suppressing the level of activated matriptase but not via altering EMT process. I also examined the effect of curcumin on the cell invasion of those cells with matriptase overexpresion. I established the stable pools of CWR22Rv1 cells with matriptase overexpression and found that expression of matriptase in CWR22Rv1 cells enhanced their invasive ability approximately one fold. With curcumin treatment, the invasive ability induced by matriptase overexpression was suppressed in a dose-dependent manner. In addition, our data also showed that curcumin was able to suppress EGF- or heregulin-stimulated PC-3 cell invasion. In summary, the data indicated that curcumin exhibits a suppressive effect on prostate cancer cell invasion, at least in part by down-regulating matriptase function.
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