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红曲菌素通过刺激内质网应激和诱导自噬来增强人前列腺癌细胞的辐射敏感性。

Monascuspiloin enhances the radiation sensitivity of human prostate cancer cells by stimulating endoplasmic reticulum stress and inducing autophagy.

机构信息

Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan.

出版信息

PLoS One. 2012;7(7):e40462. doi: 10.1371/journal.pone.0040462. Epub 2012 Jul 3.

Abstract

Prostate cancer is a very common cancer among males. Traditional treatments for prostate cancer have limited efficacy; therefore, new therapeutic strategies and/or new adjuvant drugs must be explored. Red yeast rice (RYR) is a traditional food spice made in Asia by fermenting white rice with Monascus purpureus Went yeast. Accumulating evidence indicates that RYR has antitumor activity. In this study, PC-3 cells (human prostate cancer cells) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with monascuspiloin (MP, a yellow pigment isolated from Monascus pilosus M93-fermented rice) and to determine the underlying mechanisms of these effects in vitro and in vivo. We found that IR combined with MP showed increased therapeutic efficacy when compared with either treatment alone in PC-3 cells. In addition, the combined treatment enhanced DNA damage and endoplasmic reticulum (ER) stress. The combined treatment induced primarily autophagy in PC-3 cells, and the cell death that was induced by the combined treatment was chiefly the result of inhibition of the Akt/mTOR signaling pathways. In an in vivo study, the combination treatment showed greater anti-tumor growth effects. These novel findings suggest that the combined treatment could be a potential therapeutic strategy for prostate cancer.

摘要

前列腺癌是男性中非常常见的一种癌症。前列腺癌的传统治疗方法疗效有限;因此,必须探索新的治疗策略和/或新的辅助药物。红曲米(RYR)是一种在亚洲通过用紫红曲霉酵母发酵白米制成的传统食品香料。越来越多的证据表明红曲米具有抗肿瘤活性。在本研究中,使用PC-3细胞(人前列腺癌细胞)来研究电离辐射(IR)与红曲菌素(MP,一种从红曲菌M93发酵米中分离出的黄色色素)联合使用的抗癌效果,并在体外和体内确定这些效果的潜在机制。我们发现,与单独使用任何一种治疗方法相比,IR与MP联合使用在PC-3细胞中显示出更高的治疗效果。此外,联合治疗增强了DNA损伤和内质网(ER)应激。联合治疗主要诱导PC-3细胞发生自噬,联合治疗诱导的细胞死亡主要是抑制Akt/mTOR信号通路的结果。在一项体内研究中,联合治疗显示出更大的抗肿瘤生长效果。这些新发现表明,联合治疗可能是一种潜在的前列腺癌治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1095/3389026/addc2cd87be3/pone.0040462.g001.jpg

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