Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells
<p>Abstract</p> <p>Background</p> <p>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 factor...
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doaj-945d11be119d4660981be5eea6250e822020-11-24T22:09:21ZengBMCBMC Cancer1471-24072008-07-018121810.1186/1471-2407-8-218Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cellsYu Danny CWAzahri NorZhu YongWoll Penella J<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>The levels of IL-8, VEGF and prostaglandin E<sub>2 </sub>(PGE<sub>2</sub>) 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.</p> <p>Results</p> <p>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, PGE<sub>2 </sub>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 μM for 24 or 48 h. The COX-2 activity was reduced in a dose-dependent fashion as shown by reduced PGE<sub>2 </sub>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.</p> <p>Conclusion</p> <p>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.</p> http://www.biomedcentral.com/1471-2407/8/218 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Danny CW Azahri Nor Zhu Yong Woll Penella J |
spellingShingle |
Yu Danny CW Azahri Nor Zhu Yong Woll Penella J Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells BMC Cancer |
author_facet |
Yu Danny CW Azahri Nor Zhu Yong Woll Penella J |
author_sort |
Yu Danny CW |
title |
Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells |
title_short |
Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells |
title_full |
Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells |
title_fullStr |
Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells |
title_full_unstemmed |
Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells |
title_sort |
effects of cox-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2008-07-01 |
description |
<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>The levels of IL-8, VEGF and prostaglandin E<sub>2 </sub>(PGE<sub>2</sub>) 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.</p> <p>Results</p> <p>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, PGE<sub>2 </sub>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 μM for 24 or 48 h. The COX-2 activity was reduced in a dose-dependent fashion as shown by reduced PGE<sub>2 </sub>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.</p> <p>Conclusion</p> <p>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.</p> |
url |
http://www.biomedcentral.com/1471-2407/8/218 |
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