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Int J Clin Exp Pathol 2012;5(8):796-805
Local injection of lentivirus-delivered livinshRNA suppresses lung adenocarcinoma
growth by inducing a G0/G1 phase cell cycle arrest
Yu-Sheng Chen, Hong-Ru Li, Yan Miao, Wen-Ying Chen, You-Tang Li, Gui-Qing Wang, Zheng-Cai Wu
Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Medical University; Department of Respiratory Medicine, Fujian Longyan
NO.1 Hospital, Fujian Medical University; 3Experimental animal center of Fujian Medical University, Fuzhou, Fujian, 350001, P.R.China
Received August 8, 2012; Accepted August 29, 2012; Epub October 1, 2012; Published October 15, 2012
Abstract: The inhibitor of apoptosis protein (IAP) plays an important role in tumorigenesis and may be a potential target for cancer therapy.
Livin, which belongs to this family, is highly expressed in various tumors. The previous study demonstrated that silencing Livin gene promoted
lung cancer cell apoptosis; however, the effects on tumor growth suppression by targeting this gene in vivo, to thereby determine the efficacy of
targeting Livin for patient therapy, have not been determined. This study injected lentivirus-delivered livinshRNA into established xenograft
tumors derived from the lung adenocarcinoma cell line SPC-A-1 in BALB/C nude mice, the result showed that LivinshRNA down-regulated Livin
expression effectively, induced tumor cell apoptosis, reduced tumor cell proliferation, and suppressed tumor growth dramatically, with a tumor
volume inhibitory rate of (58.65±4.82)% and a tumor weight inhibitory rate of (47.44±1.64)%, but with less severe adverse reaction to the
mouse. This study further demonstrated that Livin gene silencing induced a G0/G1-phase cell cycle arrest and cyclin D1 downregulation, which
is a key regulator of the G0/G1- to S-phase transition. These findings suggest that LivinshRNA local injection may serve as a therapeutic
method for patient treatment, and that LivinshRNA may suppress tumor growth by arresting the cell cycle in the G0/G1-phase. (IJCEP1208008).
Keywords: Livin gene, RNA interference, lung adenocarcinoma, xenograft tumor model, cell cycle
Address all correspondence to:
Dr. Yusheng Chen, Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Medical University, NO.134 East Street, Gulou
District, Fuzhou, Fujian, 350001, P.R.China. Tel: 0086-591-87557768-1023; Fax: 0086-591-87609181; E-mail: firstname.lastname@example.org