Synergistic antitumor activity of XIAP-shRNA and TRAIL expressed by oncolytic adenoviruses in experimental HCC

	Synergistic antitumor activity of XIAP-shRNA and TRAIL expressed by oncolytic adenoviruses in experimental HCC
	Pan, QW; Liu, BS; Liu, J; Cai, R; Liu, XY; Qian, C
刊名	ACTA ONCOLOGICA
	2008
卷号	47 期号:1 页码:135-144
通讯作者	Qian, C (reprint author), Zhejiang Sci Tech Univ, Sch Life Sci, Xinyuan Inst Med & Biotechnol, Hangzhou, Peoples R China.,cqian3182@sina.com.cn
英文摘要	RNA interference (RNAi) induced by small interfering RNA (siRNA) can trigger sequence-specific gene silencing in mammalian cells. It has been proposed that siRNA can be developed as a novel strategy for cancer therapy. However effective delivery of therapeutically active siRNAs into the target tissue/cells in vivo is still a major obstacle for successful application. Oncolytic adenoviral vector mediated RNAi provides the potential advantages of minimizing the harm of normal cells, regenerating siRNAs within the tumor microenvironment and inspiring an additive antitumor outcome through viral oncolysis. Hepatocellular carcinoma (HCC) displays a high resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell death, partially due to high expression levels of the X-linked Inhibitor-of-Apoptosis protein (XIAP). Here, we utilized an oncolytic adenovirus (ZD55) for expressing short hairpin RNA (shRNA), a precursor of siRNA, to knockdown XIAP. To increase sensitivity of HCC cells to TRAIL, we have used ZD55 to deliver both XIAP-shRNA and TRAIL into HCC cells. The results showed taht the combination of ZD55-XIAP-shRNA and ZD55-TRAIL resulted in significant reduction of XIAP expression and potent antitumor activity both in HCC cells and in animal model with tumor. This pilot study offers a promise of using oncolytic adenovirus to deliver siRNA targeting overexpressed oncogenes and a novel strategy for cancer therapy by regulating the equilibrium between the proapoptotic and antiapoptotic factors.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	REPLICATION-SELECTIVE ADENOVIRUS ; LIGAND-INDUCED APOPTOSIS ; X-LINKED INHIBITOR ; NEURONS IN-VIVO ; RNA INTERFERENCE ; MAMMALIAN-CELLS ; MEDIATED APOPTOSIS ; DL1520 ONYX-015 ; HUMAN-MELANOMA ; CANCER-CELLS
收录类别	SCI
语种	英语
WOS记录号	WOS:000252311700018
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1323]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Pan, QW,Liu, BS,Liu, J,et al. Synergistic antitumor activity of XIAP-shRNA and TRAIL expressed by oncolytic adenoviruses in experimental HCC[J]. ACTA ONCOLOGICA,2008,47(1):135-144.
APA	Pan, QW,Liu, BS,Liu, J,Cai, R,Liu, XY,&Qian, C.(2008).Synergistic antitumor activity of XIAP-shRNA and TRAIL expressed by oncolytic adenoviruses in experimental HCC.ACTA ONCOLOGICA,47(1),135-144.
MLA	Pan, QW,et al."Synergistic antitumor activity of XIAP-shRNA and TRAIL expressed by oncolytic adenoviruses in experimental HCC".ACTA ONCOLOGICA 47.1(2008):135-144.