Abstract

BackgroundCyclooxygenase2 (COX-2), one isoform of cyclooxygenase proinflammatory enzymes, is responsible for tumor development, invasion and metastasis. Due to its role and frequent overexpression in a variety of human malignancies, including osteosarcoma, COX-2 has received considerable attention. However, the function of COX-2 in the pathogenesis of cancer is not well understood. We examined the role of COX-2 in osteosarcoma.MethodsWe employed lentivirus mediated-RNA interference technology to knockdown endogenous gene COX-2 expression in human osteosarcoma cells (SaOS2) and analyzed the phenotypical changes. The effect of COX-2 treatment on the proliferation, cell cycle, invasion and migration of the SaOS2 cells were assessed using the MTT, flow cytometry, invasion and migration assays, respectively. COX-2, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) mRNA and protein expression were detected by RT-PCR and western blotting.ResultsOur results indicate that a decrease of COX-2 expression in human osteosarcoma cells significantly inhibited the growth, decreased the invasion and migration ability of SaOS2 cells. In addition, it also reduced VEGF, EGF and bFGF mRNA and protein expression.ConclusionsThe COX-2 signaling pathway may provide a novel therapeutic target for the treatment of human osteosarcoma.

Highlights

  • Cyclooxygenase2 (COX-2), one isoform of cyclooxygenase proinflammatory enzymes, is responsible for tumor development, invasion and metastasis

  • Downregulation of COX-2 expression by LV-COX-2siRNA-1 in SaOS2 cells To explore the effect of LV-COX-2siRNA-1 on the expression of COX-2, GFP expression was observed under a fluorescent microscope in SaOS2 cells 72 h after infection with LV-COX-2siRNA-1 (Figure 2a)

  • The results indicated that LV-COX-2siRNA-1 significantly inhibited mRNA (P = 0.0001) and protein levels of COX-2 compared with the LV-Control and parental SaOS2 cells (Figure 2b)

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Summary

Introduction

Cyclooxygenase (COX-2), one isoform of cyclooxygenase proinflammatory enzymes, is responsible for tumor development, invasion and metastasis. Many reports have indicated that COX-2 expression is increased in a variety of human malignancies, including osteosarcoma, and is responsible for producing large amounts of PGE2 in tumor tissues [8,9,10,11]. These molecules are thought to play a critical role in tumor growth, because they reduce apoptotic cell death, stimulate angiogenesis and invasiveness [12,13]. Another aim of this study was to establish whether there is a direct relationship between COX-2 expression and VEGF, EGF and bFGF production in osteosarcoma cells

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