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Effects of resveratrol on vascular endothelial growth factor expression in osteosarcoma cells and cell proliferation.

ABSTRACT: The aim of the current study was to investigate the effects of resveratrol (Res) on vascular endothelial growth factor (VEGF) expression and cell proliferation in the human osteosarcoma cell line U20S. U20S cells were treated with Res at various concentrations (0, 10, 20 and 40 ?mol/l) for various times (24, 48 and 72 h). The inhibitory effect of Res on U20S proliferation was observed using methyl thiazolyl tetrazolium (MTT) colorimetry. VEGF expression was determined using real-time polymerase chain reaction (RT-PCR) and western blot analysis. The inhibitory effect of Res on U20S proliferation increased as the concentration of Res increased. The inhibitory effect also increased with time. Res had an inhibitory effect on VEGF expression and significantly inhibited U20S cell proliferation. Res may exert an anti-osteosarcoma effect by inhibiting VEGF expression in tumor cells.

SUBMITTER: Liu Z

PROVIDER: S-EPMC3506664 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Effects of resveratrol on vascular endothelial growth factor expression in osteosarcoma cells and cell proliferation.

Liu Zhonghe Z Li Yanlan Y Yang Rui R

Oncology letters 20120725 4

The aim of the current study was to investigate the effects of resveratrol (Res) on vascular endothelial growth factor (VEGF) expression and cell proliferation in the human osteosarcoma cell line U20S. U20S cells were treated with Res at various concentrations (0, 10, 20 and 40 μmol/l) for various times (24, 48 and 72 h). The inhibitory effect of Res on U20S proliferation was observed using methyl thiazolyl tetrazolium (MTT) colorimetry. VEGF expression was determined using real-time polymerase ...[more]

PMID: 23205110

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Project description:BACKGROUND: Cyclooxygenase (COX)-2 has been implicated in tumour progression, angiogenesis and metastasis in non-small cell lung cancer (NSCLC). We speculated that inhibition of COX-2 activity might reduce expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in lung cancer cells. METHODS: The levels of IL-8, VEGF and prostaglandin E2 (PGE2) were measured by ELISA. Expression of COX-1 and COX-2 was determined by Western blotting. Inhibition or knockdown of COX-2 was achieved by treating NSCLC cells with specific COX-2 inhibitor NS-398 or COX-2 siRNA, respectively. RESULTS: We found that NSCLC cell lines produced more IL-8 than VEGF (p < 0.001). In contrast, small cell lung cancer (SCLC) cell lines produced more VEGF than IL-8 (p < 0.001). COX-1 was expressed in all cell lines, but COX-2 was expressed only in NSCLC cell lines. Consistent with this, PGE2 was significantly higher in NSCLC cell lines than SCLC cell lines (p < 0.001). We tested these cell lines with a potent specific COX-2 inhibitor NS-398 at concentrations of 0.02, 0.2, 2, 20 microM for 24 or 48 h. The COX-2 activity was reduced in a dose-dependent fashion as shown by reduced PGE2 production. VEGF was significantly reduced following the treatment of NS-398 in A549 (by 31%) and MOR/P (by 47%) cells lines which expressing strong COX-2, but not in H460 cell line which expressing very low COX-2. However, IL-8 was not reduced in these cell lines. To confirm these results, we knocked down COX-2 expression with COX-2 siRNA in these cell lines. VEGF was significantly decreased in A549 (by 24%) and in MOR/P (by 53%), but not in H460 whereas IL-8 was not affected in any cell line. CONCLUSION: We conclude that NSCLC cells produce much higher levels of IL-8 than SCLC cells whereas both NSCLC and SCLC cells produce similar levels of VEGF. COX-2 is only expressed in NSCLC cells, but not in SCLC cells. VEGF is produced in both NSCLC and SCLC cells regardless of COX-2 expression. However, VEGF production is, at least partly, COX-2 dependent in NSCLC cells expressing COX-2. In contrast, IL-8 production is COX-2 independent in both NSCLC and SCLC cells. We speculate that combined targeting of COX-2 and IL-8 may be useful in the treatment of patients with NSCLC and targeting VEGF may be useful in the treatment of patients with SCLC.

Dataset Information

Effects of resveratrol on vascular endothelial growth factor expression in osteosarcoma cells and cell proliferation.

Publications

Effects of resveratrol on vascular endothelial growth factor expression in osteosarcoma cells and cell proliferation.

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