Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth

	Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth
	He, GQ; Lei, W; Wang, SB; Xiao, RJ; Guo, KN; Xia, YL; Zhou, XM; Zhang, KJ; Liu, XY; Wang, YG
刊名	JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
	2012
卷号	138 期号:4 页码:657-670
关键词	Oncolytic adenovirus TSLC1 Hepatocellular carcinoma Caspase pathway
通讯作者	Liu, XY (reprint author), Zhejiang Sci Tech Univ, Xinyuan Inst Med & Biotechnol, Sch Life Sci, 2 Rd Xiasha Dist, Hangzhou 310018, Peoples R China.,xyliu@sibs.ac.cn ; wangyigang43@163.com
英文摘要	Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Oncolytic viruses represent a promising therapeutic agent or vehicle to human cancers due to their ability of selectively lysing cancer cells but not in normal cells. TSLC1, a novel tumor suppressor gene, was loss in many human cancers including HCC, not in normal cells. The current study is focused on the antitumor effect of TSLC1-armed survivin-regulated oncolytic adenovirus for HCC and to explore their molecular mechanism. The expression of tumor suppressor TSLC1 and survivin was detected by quantitative PCR. The recombinant virus Ad.SP-E1A-E1B((Delta 55))-TSLC1 (brief name as SD55-TSLC1) was constructed by inserting TSLC1 gene into the dual-regulated oncolytic adenovirus vector Ad.SP-E1A-E1B((Delta 55)). Then, we performed the antitumor experiments of SD55-TSLC1 in vitro and in nude mice xenografted with Huh7 liver cancer. The expression of TSLC1 was lower in HCC cells than in normal cells, which implied TSLC1 is a tumor suppressor of liver cancer. Survivin expression is higher in detected HCC cells than in normal cells. The SD55-TSLC1 exhibited an excellent antitumor effect on HCC cell growth in vitro but does no or little damage to normal liver cells. Animal experiment further confirmed that SD55-TSLC1 achieved significant inhibition of Huh7 liver cancer xenografted growth. Furthermore, the mechanism of antitumor efficacy by SD55-TSLC1 was elucidated to be due to the activation of caspase apoptotic pathway including the inducement of caspase-3, caspase-8, and poly (ADP-ribose) polymerase cleavage. This is the first report of TSLC1 by oncolytic adenovirus with an excellent antitumor effect to liver cancer growth. These data suggest that an oncolytic adenovirus expressing TSLC1 is effective and support that SD55-TSLC1 may be a potent antitumoral agent for future clinical trials of liver cancer.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	POTENT ANTITUMOR-ACTIVITY ; CELL LUNG-CANCER ; NASOPHARYNGEAL CARCINOMA ; PROMOTER METHYLATION ; ADHESION MOLECULE ; DNA METHYLATION ; GASTRIC-CANCER ; IN-VIVO ; GENE ; EXPRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000301836000013
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/582]
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	He, GQ,Lei, W,Wang, SB,et al. Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth[J]. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY,2012,138(4):657-670.
APA	He, GQ.,Lei, W.,Wang, SB.,Xiao, RJ.,Guo, KN.,...&Wang, YG.(2012).Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth.JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY,138(4),657-670.
MLA	He, GQ,et al."Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth".JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 138.4(2012):657-670.