Abstract
BackgroundAP-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.MethodsTwo 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.ResultsThe 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-xL was inhibited. It didn't induce cell cycle arrest when AP-4 was knockdown in p53 defect gastric cancer cell line Kato-III.ConclusionsThese 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.
Highlights
The incidence and mortality rates associated with gastric cancer have gradually decreased in recent years in most areas of the world [1,2], gastric cancer remains a worldwide health burden, and remains the most common cause of cancer related deaths with little improvement of long-term survival
We reported previously that AP-4 was overexpressed in gastric cancer and that it may be associated with the poor prognosis [30]
The mRNA and protein levels of AP-4 were decreased with AP-4 siRNA transfection group but not in the control siRNA (Figure 1)
Summary
The incidence and mortality rates associated with gastric cancer have gradually decreased in recent years in most areas of the world [1,2], gastric cancer remains a worldwide health burden, and remains the most common cause of cancer related deaths with little improvement of long-term survival. More than one million new cases were diagnosed each year, especially in East Asia, like Japan, Korea, and China. In these countries, gastric cancer remains the most common cause of cancer related deaths, and the precise pathogenesis remains unknown [3]. 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
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