Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-gamma-induced apoptosis

	Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-gamma-induced apoptosis
	Li, J; Shen, F; Wu, D; Wei, LX; Wang, YZ; Shi, LH; Zou, Y; Wu, MC
刊名	ONCOLOGY REPORTS
	2007
卷号	17 期号:5 页码:1067-1075
关键词	Bcl-XL hepatocellular carcinoma LIGHT interferon-gamma apoptosis
通讯作者	Shen, F (reprint author), Second Mil Med Univ, Div Comprehens Treatment, Eastern Hepatobiliary Hosp, 225 Changhai Rd, Shanghai 200438, Peoples R China.,shenfengdfgd@yahoo.com.cn
英文摘要	The molecular mechanisms of apoptosis caused by IFN-gamma (interferon gamma)/LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells) have not been studied in detail. The present study was undertaken to. gain insights into the signaling pathways involved in apoptosis induced by IFN-gamma/LIGHT in hepatocellular carcinoma (HCC) cell lines. Cell proliferation assay, flow cytometry, Western blotting, gene transfer and RNA interference were used in this study. LIGHT enhanced IFN-gamma-mediated apoptosis in Hep3B cells. IFN-gamma/LIGHT-induced apoptosis was inhibited by blocking peptides to the lymphotoxin beta receptor (LT-beta R), and not by the herpes virus entry mediator (HVEM). Expression of LT-beta R remained unchanged after cytokine treatments. IFN-gamma/LIGHT treatment resulted in the down-regulation of Bcl-XL and the activation of caspase-9 and caspase-3 as well as the decrease of phosphorylation of STAT3. HepG2 and SMMC-7721 cells, which showed high levels of endogenous Bcl-XL, displayed resistance to IFN-gamma/LIGHT-induced apoptosis. Overexpression of Bcl-XL in Hep3B cells increased the resistance to IFN-gamma/LIGHT induced apoptosis while the down-regulation of Bcl-XL in HepG2 and SMMC-7721 cells by RNA interference decreased the resistance. Our study provides important mechanistic insights into IFN-gamma/LIGHT-induced apoptosis in HCC cells and may help to select better therapeutic strategies for certain cancers with distinct Bcl-XL expression.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	LYMPHOTOXIN-BETA-RECEPTOR ; TUMOR-NECROSIS-FACTOR ; HERPESVIRUS ENTRY MEDIATOR ; VERSUS-HOST-DISEASE ; KAPPA-B FAMILY ; T-CELLS ; TNF SUPERFAMILY ; CANCER-CELLS ; MEMBER ; DEATH
收录类别	SCI
语种	英语
WOS记录号	WOS:000245855800014
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1570]
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	Li, J,Shen, F,Wu, D,et al. Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-gamma-induced apoptosis[J]. ONCOLOGY REPORTS,2007,17(5):1067-1075.
APA	Li, J.,Shen, F.,Wu, D.,Wei, LX.,Wang, YZ.,...&Wu, MC.(2007).Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-gamma-induced apoptosis.ONCOLOGY REPORTS,17(5),1067-1075.
MLA	Li, J,et al."Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-gamma-induced apoptosis".ONCOLOGY REPORTS 17.5(2007):1067-1075.