Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclooxygenase-2 (COX-2) inhibitors exert antitumor activity via COX-2-dependent and independent pathways. We wished to evaluate the antitumor activity of meloxicam, a preferential COX-2 inhibitor, in osteosarcoma, the most common primary malignant bone tumor, and determine whether its antitumor effect is COX-2-dependent. COX-2 expression in the osteosarcoma cell lines MG-63, HOS and U2-OS was determined by real-time RT-PCR and western blotting. Subsequently, the inhibitory effects of meloxicam on osteosarcoma cell growth and invasiveness were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and matrigel invasion assays, respectively. Apoptotic activity was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining and semi-quantification of Bax and Bcl-2 expression by real time RT-PCR and western blotting. Prostaglandin-E(2) (PGE(2)) production in the presence and absence of meloxicam was analyzed by enzyme immunoassay, and to determine whether the effects of meloxicam are COX-2-dependent or independent, PGE(2) was added to see if it reversed the effects of meloxicam. In addition, the effects of meloxicam on tumor growth and metastasis were evaluated in an in vivo mouse model using grafted LM-8 mouse osteosarcoma cells, together with immunohistochemical analysis for vascular endothelial growth factor in lung metastatic lesion. Meloxicam inhibited PGE(2) production, proliferation and invasiveness especially in MG-63 cells, which express relatively high levels of COX-2. Only high concentrations of meloxicam caused apoptosis and upregulated Bax mRNA and protein in MG-63 cell culture. In contrast, meloxicam did not induce apoptosis in HOS and U2-OS cells, expressing relatively low levels of COX-2. Exogenous PGE(2) reduced the effects of meloxicam on cell viability and invasiveness, but not its effect on Bax mRNA. In vivo, high doses of meloxicam suppressed LM-8 tumor growth and lung metastasis. Meloxicam, may have both COX-2-dependent and independent inhibitory actions on osteosarcoma. Its effects are more prominent in osteosarcoma cells that have relatively high levels of COX-2.
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PMID:Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes. 1621 34

The effect of the proinflammatory cytokine interleukin (IL)-1beta on the cellular proliferation of human osteoblastic cells (SaM-1) and osteosarcoma-derived cells (SaOS-2, HOS, and MG-63) was examined. IL-1beta stimulated the proliferation of SaM-1 and MG-63 cells, but had no effect on that of SaOS-2 or HOS cells. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, the mRNA expression of IL-1 receptor type I (IL-1R1) was detected in SaM-1 and MG-63 cells consistently, but not in SaOS-2 or HOS cells in the proliferative stage. Neither the decoy inhibitory IL-1 receptor type II (IL-1R2) nor IL-1R antagonist mRNA was detected in any of the cell lines, suggesting that IL-1beta stimulated proliferation via IL-1R1. The IL-1beta -stimulated proliferation was inhibited by the MAPK kinase (MEK) inhibitor PD98059 but not by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 or the cyclooxygenase-2 specific inhibitor NS-398, suggesting that IL-1beta stimulated proliferation via MEK, without affecting prostaglandin E(2) synthesis. IL-1beta stimulated cellular proliferation but inhibited the synthesis of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OSCAL). Both the increased proliferation and decreased Gla-OSCAL synthesis were suppressed by vitamin K(2) (VK(2)), which is a cofactor for gamma-carboxylase. Furthermore, the inhibitory effect of VK(2) on IL-1beta -stimulated proliferation was suppressed by warfarin. However, rifampicin the nuclear receptor steroid and xenobiotic receptor (SXR) ligand had no effect of IL-beta, suggesting that IL-1beta is involved in VK(2) dependent gamma-calboxylation but not SXR-activation. These results suggest that IL-1beta stimulated cellular proliferation via MEK and inhibited Gla-OSCAL synthesis, which were both inhibited by VK(2) via gamma-carboxylation.
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PMID:Inhibitory effect of vitamin K(2) on interleukin-1beta-stimulated proliferation of human osteoblasts. 2046 Jul 58