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Down-regulation of AP-4 inhibits proliferation, induces cell cycle arrest and promotes apoptosis in human gastric cancer cells.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (5), pp. e37096. Date of Electronic Publication: 2012 May 16. - Publication Year :
- 2012
-
Abstract
- Background: AP-4 belongs to the basic helix-loop-helix leucine-zipper subgroup; it controls target gene expression, regulates growth, development and cell apoptosis and has been implicated in tumorigenesis. Our previous studies indicated that AP-4 was frequently overexpressed in gastric cancers and may be associated with the poor prognosis. The purpose of this study is to examine whether silencing of AP-4 can alter biological characteristics of gastric cancer cells.<br />Methods: Two specific siRNAs targeting AP-4 were designed, synthesized, and transfected into gastric cancer cell lines and human normal mucosa cells. AP-4 expression was measured with real-time quantitative PCR and Western blot. Cell proliferation and chemo-sensitivity were detected by CCK-8 assay. Cell cycle assay and apoptosis assay were performed by flow cytometer, and relative expression of cell cycle regulators were detected by real-time quantitative PCR and Western blot, expression of the factors involved in the apoptosis pathway were examined in mRNA and protein level.<br />Results: The expression of AP-4 was silenced by the siRNAs transfection and the effects of AP-4 knockdown lasted 24 to 96 hrs. The siRNA-mediated silencing of AP-4 suppressed the cellular proliferation, induced apoptosis and sensitized cancer cells to anticancer drugs. In addition, the expression level of p21, p53 and Caspase-9 were increased when AP-4 was knockdown, but the expression of cyclin D1, Bcl-2 and Bcl-x(L) was inhibited. It didn't induce cell cycle arrest when AP-4 was knockdown in p53 defect gastric cancer cell line Kato-III.<br />Conclusions: These results illustrated that gene silencing of AP-4 can efficiently inhibited cell proliferation, triggered apoptosis and sensitized cancer cells to anticancer drugs in vitro, suggesting that AP-4 siRNAs mediated silencing has a potential value in the treatment of human gastric cancer.
- Subjects :
- Adaptor Protein Complex 4 metabolism
Caspase 9 genetics
Caspase 9 metabolism
Cell Growth Processes genetics
Cell Line, Tumor
Cyclin D1 genetics
Cyclin D1 metabolism
Cyclin-Dependent Kinase Inhibitor p21 genetics
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger genetics
RNA, Small Interfering genetics
Stomach Neoplasms metabolism
bcl-X Protein genetics
bcl-X Protein metabolism
Adaptor Protein Complex 4 genetics
Apoptosis genetics
Cell Cycle Checkpoints genetics
Stomach Neoplasms genetics
Stomach Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22615908
- Full Text :
- https://doi.org/10.1371/journal.pone.0037096