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Local injection of lentivirus-delivered livinshRNA suppresses lung adenocarcinoma growth by inducing a G0/G1 phase cell cycle arrest.
- Source :
-
International journal of clinical and experimental pathology [Int J Clin Exp Pathol] 2012; Vol. 5 (8), pp. 796-805. Date of Electronic Publication: 2012 Oct 01. - Publication Year :
- 2012
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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.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma of Lung
Animals
Apoptosis
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Female
Gene Expression Regulation, Neoplastic drug effects
Gene Silencing
Gene Transfer Techniques
Humans
Lentivirus genetics
Lung Neoplasms genetics
Male
Mice
Mice, Inbred BALB C
Mice, Nude
RNA Interference
Xenograft Model Antitumor Assays
Adaptor Proteins, Signal Transducing genetics
Adenocarcinoma pathology
G1 Phase Cell Cycle Checkpoints drug effects
Genetic Therapy methods
Inhibitor of Apoptosis Proteins genetics
Lung Neoplasms pathology
Neoplasm Proteins genetics
RNA, Small Interfering pharmacology
Resting Phase, Cell Cycle drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1936-2625
- Volume :
- 5
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- International journal of clinical and experimental pathology
- Publication Type :
- Academic Journal
- Accession number :
- 23071862