BMC Cancer | |
Survivin gene silencing sensitizes prostate cancer cells to selenium growth inhibition | |
Research Article | |
Yan Dong1  Lijuan Zhao2  Xuejian Zhao2  Lifang Gao2  Yanying Zhao2  Xichun Liu3  Haitao Zhang4  Ruijuan Gao5  | |
[1] Department of Structural and Cellular Biology, Tulane University School of Medicine, 1430 Tulane Avenue, 70112, New Orleans, LA, USA;Molecular Signaling Program, Louisiana Cancer Research Consortium, 1615 Poydras Street, Suite 1000, 70112, New Orleans, LA, USA;Prostate Diseases Prevention and Treatment Research Center and Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Xinmin Street, 130021, Changchun, PR, China;Prostate Diseases Prevention and Treatment Research Center and Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Xinmin Street, 130021, Changchun, PR, China;Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, 70112, New Orleans, LA, USA;Prostate Diseases Prevention and Treatment Research Center and Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Xinmin Street, 130021, Changchun, PR, China;Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, 70112, New Orleans, LA, USA;Molecular Signaling Program, Louisiana Cancer Research Consortium, 1615 Poydras Street, Suite 1000, 70112, New Orleans, LA, USA;Prostate Diseases Prevention and Treatment Research Center and Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Xinmin Street, 130021, Changchun, PR, China;Department of Structural and Cellular Biology, Tulane University School of Medicine, 1430 Tulane Avenue, 70112, New Orleans, LA, USA; | |
关键词: Prostate Cancer; Selenium; Prostate Cancer Cell; Prostate Cancer Cell Line; Survivin Expression; | |
DOI : 10.1186/1471-2407-10-418 | |
received in 2009-07-07, accepted in 2010-08-10, 发布年份 2010 | |
来源: Springer | |
【 摘 要 】
BackgroundProstate cancer is a leading cause of cancer-related death in men worldwide. Survivin is a member of the inhibitor of apoptosis (IAP) protein family that is expressed in the majority of human tumors including prostate cancer, but is barely detectable in terminally differentiated normal cells. Downregulation of survivin could sensitize prostate cancer cells to chemotherapeutic agents in vitro and in vivo. Selenium is an essential trace element. Several studies have shown that selenium compounds inhibit the growth of prostate cancer cells. The objective of this study is to investigate whether survivin gene silencing in conjunction with selenium treatment could enhance the therapeutic efficacy for prostate cancer and to elucidate the underlying mechanisms.MethodsExpression of survivin was analyzed in a collection of normal and malignant prostatic tissues by immunohistochemical staining. In vitro studies were conducted in PC-3M, C4-2B, and 22Rv1 prostate cancer cells. The effect of selenium on survivin expression was analyzed by Western blotting and semi-quantitative RT-PCR. Survivin gene knockdown was carried out by transfecting cells with a short hairpin RNA (shRNA) designed against survivin. Cell proliferation was quantitated by the 3-(4,5-Dimethylthiazol-2-yl)- 2,5-Diphenyltetrazolium Bromide (MTT) assay and apoptosis by propidium iodide staining followed by flow cytometry analysis. Finally, in vivo tumor growth assay was performed by establishing PC-3M xenograft in nude mice and monitoring tumor growth following transfection and treatment.ResultsWe found that survivin was undetectable in normal prostatic tissues but was highly expressed in prostate cancers. Survivin knockdown or selenium treatment inhibited the growth of prostate cancer cells, but the selenium effect was modest. In contrast to what have been observed in other cell lines, selenium treatment had little or no effect on survivin expression in several androgen-independent prostate cancer cell lines. Survivin knockdown sensitized these cells to selenium growth inhibition and apoptosis induction. In nude mice bearing PC-3M xenografts, survivin knockdown synergizes with selenium in inhibiting tumor growth.ConclusionsSelenium could inhibit the growth of hormone-refractory prostate cancer cells both in vitro and in vivo, but the effects were modest. The growth inhibition was not mediated by downregulating survivin expression. Survivin silencing greatly enhanced the growth inhibitory effects of selenium.
【 授权许可】
Unknown
© Liu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
【 预 览 】
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