前列腺癌為歐美國家男性常見的癌症，並在近幾年成為台灣男性十大癌症之一。放射線治療為前列腺癌治療最常見的方式，但使用高劑量放射線卻會導致許多副作用，例如:性功能及泌尿道障礙等。近年來有許多研究發現天然物具有預防或治療疾病的效果。根據文獻的研究報導，紅麴代謝產物具有抑制膽固醇合成、抗氧化及抗癌的功效。因此，本研究的目的之一乃希望藉由合併紅麴的方式增加前列腺癌細胞對於放射線治療的效果，並探討其相關作用機轉，同時也評估紅麴是否具有預防前列腺相關疾病之功效。實驗分細胞及動物實驗兩部分:1.採用人類前列腺癌細胞株(PC-3)進行紅麴合併放射線之試驗，以trypan blue計算細胞存活率，並利用流式細胞儀分析細胞週期、早期細胞凋亡以及自體吞噬，彗星試驗觀察基因損傷程度，並以西方墨點法分析自體吞噬、基因損傷及內質網壓力等相關機轉蛋白之表現量變化。2.動物實驗則使用六至八周大Spraque-Dawley品系之公鼠，並以雄性素及致癌劑誘發前列腺肥大或前列腺癌，待犧牲後計算大鼠之前列腺比(前列腺重/體重)並以切片觀察各組前列腺之病理變化並利用酵素連結免疫吸附分析法分析指標蛋白。研究結果顯示，相較於單獨處理放射線及紅麴，兩者的合併更可提高PC-3死亡率，但合併處理組其細胞凋亡情況與單獨處理組並無太大差異，然而合併組卻顯著提高自體吞噬及基因損傷的情形。於裸鼠腫瘤模式中發現，紅麴與放射線的合併可抑制約70%腫瘤生長。另外在前列腺肥大化學預防之實驗中發現，飼料中添加紅麴之組別其前列腺與體重的比值相較於沒有添加紅麴之組別較低，且可降低前列腺特定抗原含量，並於組織切片及染色後觀察到前列腺上皮之生長較為正常；另外於原位大鼠前列腺癌試驗中發現紅麴不僅可有效降低血液中三酸甘油酯及總膽固醇，更可降低血液中雙氫睪固酮的含量進而減少罹患前列腺癌的風險。綜合上述研究，證實紅麴不僅可提高放射線對於前列腺癌之治療效果，亦具有預防前列腺相關疾病發生之功效。

Prostate cancer is one of the most common tumors among men in United State. Radiotherapy is one of the treatments for prostate cancer. Recently, Monascus has been reported possessing anticholesterol, antihypertension and antiproliferation effects on prostate cancer. The aims of this study were to investigate the mechanisms of anticancer effect of irradiation (IR) combined with Monascus on prostate cancer cells and evaluate the chemopreventive effects of Monascus on prostate-related disease. Both cell culture and animal experiments were applied in our study. In in vitro study, PC-3 cells were used to analyze the effects of Monascus combined with IR. Cell viability was counted by trypan blue. Cell cycle and apoptosis were analyzed by flow cytometry. DNA damage level was observed by comet assay. Western blotting was used to determine pathway-related protein expression. In in vivo animal study, SD rats were treated with testosterone and/or carcinogen to induce benign prostatic hypertrophy and prostate cancer. By the end of experiments, we calculated the prostate size ratio of rats and determined the biochemical index 、pathological changes and prostate specific antigen ELISA kits. The results indicated that the cytotoxicity of combined treatment is more effective than IR or Monascus alone in PC-3 cells. Although the combined treatment did not increase the percentage of apoptosis, it enhanced autophagy significantly. Furthermore, combined treatment caused more DNA damage and ER stress than IR or Monascus alone. In xenograft model, the combined treatment group had a 70% reduction in tumor size compared with positive control group. In the in vivo chemopreventive animal studies, we found that the prostate size ratio, PSA (prostate specific antigen), triglyceride, total cholesterol and dihydrotestosterone of rats treated with Monascus were significantly lower than the positive control group. Our data suggested that Monascus, which is used in traditional medicine for the treatment of various ailments, may enhance the radiosensitivity of PC-3 cells and could be effective in prevention of prostate-related disease.

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