靶向Bcl-2可克服前列腺癌细胞对XIAP基因下调的适应性。
Molecular targeting of Bcl-2 overcomes prostate cancer cell adaptation to XIAP gene downregulation.
作者信息
Nakano Y, Bilim V, Yuuki K, Muto A, Kato T, Nagaoka A, Tomita Y
机构信息
Department of Urology, Yamagata University School of Medicine, Yamagata, Japan.
出版信息
Prostate Cancer Prostatic Dis. 2009;12(1):34-40. doi: 10.1038/pcan.2008.27. Epub 2008 May 13.
X-linked inhibitor of apoptosis (XIAP) is a suppressor of apoptosis that supports an increased survival and resistance to chemotherapy of human prostate cancer (PCa) cells. Effects of transient (24 h) and chronic (beyond 1 month) downregulation of XIAP in DU145 hormone refractory prostate cancer (HRPC) cells were studied. We found that transient downregulation of XIAP by siRNAs resulted in an increase of apoptosis and a decrease in Bcl-2 levels and sensitized PCa cells to cisplatin. XIAP downregulation by shRNA vector stable transfection led to upregulation of Bcl-2 protein. Our results identify the adaptability of PCa cells to chronic loss of XIAP in part through upregulation of Bcl-2 and indicate that multitargeting approach is the most effective application in the chemotherapy of human HRPC.
X连锁凋亡抑制蛋白（XIAP）是一种凋亡抑制因子，可提高人前列腺癌细胞（PCa）的存活率并增强其对化疗的抗性。我们研究了在DU145激素难治性前列腺癌（HRPC）细胞中短暂（24小时）和长期（超过1个月）下调XIAP的效果。我们发现，通过小干扰RNA（siRNAs）短暂下调XIAP会导致细胞凋亡增加、Bcl-2水平降低，并使PCa细胞对顺铂敏感。通过短发夹RNA（shRNA）载体稳定转染下调XIAP会导致Bcl-2蛋白上调。我们的研究结果表明，PCa细胞可通过上调Bcl-2来部分适应XIAP的长期缺失，这表明多靶点方法在人类HRPC化疗中是最有效的应用方式。
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