Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells

Hu,Jianwu; Chen,Caiyun; Su,Yuan; Du,Jiao; Qian,Xin; Jin,Yang

doi:10.3892/etm.2012.702

Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells

Authors:
- Jianwu Hu
- Caiyun Chen
- Yuan Su
- Jiao Du
- Xin Qian
- Yang Jin
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Affiliations: Department of Pulmonary Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China
Published online on: September 10, 2012 https://doi.org/10.3892/etm.2012.702
Pages: 1045-1050

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Abstract

Vascular endothelial growth factor (VEGF) plays a critical role in tumor progression, angiogenesis and metastasis. Cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)2, MMP9 and wild-type (WT) p53 has been found to regulate the production of VEGF. Whether VEGF regulates the production of COX-2, MMP2, MMP9 and WTp53, however, has yet to be determined. This study examined the influence of the overexpression or knockdown of VEGF on the protein levels of COX-2, MMP2, MMP9 and WTp53 as well as cell growth and cell cycle progression in Lewis lung carcinoma (LLC) cells. LLC cells were transfected with pIRES2-VEGF-GFP in the VEGF-overexpressing group (LLC-VEGF), pIRES2‑GFP in the mock group (LLC-GFP) or pSUPER-VEGF-GFP in the VEGF knockdown group (LLC-RNAi). Protein levels were detected by western blot analysis. LLC cell growth exhibited no marked change in the LLC-VEGF group, but was significantly retarded in the LLC-RNAi group. Further examination revealed that more cells entered the S stage in the LLC-VEGF group than in the control (or mock) group (45.3 vs. 29.1%, P<0.05), and that cell growth was retarded in the LLC-RNAi group. Moreover, COX-2 and MMP2 and MMP9 proteins were significantly increased in the LLC-VEGF group (approximately 1.84-, 1.89- and 1.83-fold, respectively, vs. control, P<0.05), but significantly decreased in the LLC-RNAi group, whereas the expression of WTp53 exhibited the opposite pattern of change. VEGF expression was positively correlated with COX-2, MMP2 and MMP9 expression (r=0.984, r=0.978, r=0.969, respectively, P<0.01) and negatively correlated with WTp53 (r=-0.833, p<0.01). The activities of MMP2 and MMP9 were increased in the LLC-VEGF group. In conclusion, VEGF overexpression may promote the expression of COX-2 and MMPs, but inhibits WTp53 production in LLC cells; VEGF underexpression may have an inverse effect. These changes are closely correlated with the infiltration and metastasis of lung cancer.

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