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Article

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
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China
  • Pages: 1045-1050
    |
    Published online on: September 10, 2012
       https://doi.org/10.3892/etm.2012.702
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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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1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar

2 

Brundage MD, Davies D and Mackillop WJ: Prognostic factors in non-small cell lung cancer: a decade of progress. Chest. 122:1037–1057. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Folkman J: Clinical applications of research on angiogenesis. N Engl J Med. 333:1757–1763. 1995. View Article : Google Scholar : PubMed/NCBI

4 

Saphir A: Angiogenesis the unifying concept in cancer. J Natl Cancer Inst. 89:1658–1659. 1995.PubMed/NCBI

5 

Chen HJ, Treweeke AT, Ke YQ, West DC and Toh CH: Angiogenically active vascular endothelial growth factor is over-expressed in malignant human and rat prostate carcinoma cells. Br J Cancer. 82:1694–1701. 2000.PubMed/NCBI

6 

George ML, Tutton MG, Janssen F, Arnaout A, Abulafi AM, Eccles SA and Swift RI: VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia. 3:420–427. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Nishida N, Yano H, Komai K, Nishida T, Kamura T and Kojiro M: Vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 are related closely to the prognosis of patients with ovarian carcinoma. Cancer. 101:1364–1374. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Ohta Y, Endo Y, Tanaka M, Shimizu J, Oda M, Hayashi Y, Watanabe Y and Sasaki T: Significance of vascular endothelial growth factor messenger RNA expression in primary lung cancer. Clin Cancer Res. 2:1411–1416. 1996.PubMed/NCBI

9 

Jin Y, Xiong X, Su Y, Hu J and Tao X: Serum vascular endothelial growth factor levels in patients with non-small cell lung cancer and its relations to the micrometastasis in peripheral blood. J Huazhong Univ Sci Technolog Med Sci. 29:462–465. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y and Hirohashi S: Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma. Clin Cancer Res. 6:2431–2439. 2000.PubMed/NCBI

11 

Smith WL and Langenbach R: Why there are two cyclooxygenase isozymes. J Clin Invest. 107:1491–1495. 2011. View Article : Google Scholar

12 

Lim SC, Park SY and Do NY: Correlation of cyclooxygenase-2 pathway and VEGF expression in head and neck squamous cell carcinoma. Oncol Rep. 10:1073–1079. 2003.PubMed/NCBI

13 

Von Rahden BH, Stein HJ, Pühringer F, Koch I, Langer R, Piontek G, Siewert JR, Höfler H and Sarbia M: Coexpression of cyclooxygenases (COX-1, COX-2) and vascular endothelial growth factors (VEGF-A, VEGF-C) in esophageal adenocarcinoma. Cancer Res. 65:5038–5044. 2005.PubMed/NCBI

14 

Cianchi F, Cortesini C, Bechi P, Fantappiè O, Messerini L, Vannacci A, Sardi I, Baroni G, Boddi V, Mazzanti R and Masini E: Up-regulation of cyclooxygenase-2 gene expression correlates with tumour angiogenesis in human colorectal cancer. Gastroenterology. 121:1339–1347. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Huang SP, Wu MS, Shun CT, Wang HP, Hsieh CY, Kuo ML and Lin JT: Cyclooxygenase-2 increases hypoxia inducible factor-1 and vascular endothelial growth factor to promote angiogenesis in gastric carcinoma. J Biomed Sci. 12:229–241. 2005. View Article : Google Scholar

16 

Dirim A, Haberal AN, Goren MR, Tekin MI, Peskircioglu L, Demirhan B and Ozkardes H: VEGF, COX-2, and PCNA expression in renal cell carcinoma subtypes and their prognostic value. Int Urol Nephrol. 40:861–868. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Kim HS, Youm HR, Lee JS, Min KW, Chung JH and Park CS: Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell lung cancer. Lung Cancer. 42:163–170. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Rundhaug JE: Matrix metalloproteinases and angiogenesis. J Cell Mol Med. 9:267–285. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Rooprai HK, Rucklidge GJ, Panou C and Pilkington GJ: The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumor cells. Br J Cancer. 82:52–55. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Lee KS, Min KH, Kim SR, Park SJ, Park HS, Jin GY and Lee YC: Vascular endothelial growth factor modulates matrix metalloproteinase-9 expression in asthma. Am J Respir Crit Care Med. 174:161–170. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Zilfou JT and Lowe SW: Tumor suppressive functions of p53. Cold Spring Harb Perspect Biol1. a001883 View Article : Google Scholar : 2009.PubMed/NCBI

22 

Mukhopadhyay D, Tsiokas L and Sukhatme VP: Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res. 55:6161–6165. 1995.PubMed/NCBI

23 

Birk DM, Barbato J, Mureebe L and Chaer RA: Current insights on the biology and clinical aspects of VEGF regulation. Vasc Endovascular Surg. 42:517–530. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Dvorak HF, Brown LF, Detmar M and Dvorak AM: Vascular permeability factor/vascular endothelial growth factor, micro-vascular hyperpermeability, and angiogenesis. Am J Pathol. 146:1029–1039. 1995.PubMed/NCBI

25 

Fujio Y and Walsh K: Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner. J Biol Chem. 274:16349–16354. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Claffey KP, Brown LF, del Aguila LF, Tognazzi K, Yeo KT, Manseau EJ and Dvorak HF: Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res. 56:172–181. 1996.

27 

Miyata Y, Koga S, Kanda S, Nishikido M, Hayashi T and Kanetake H: Expression of cyclooxygenase-2 in renal cell carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, expression of matrix metalloproteinase-2, and survival. Clin Cancer Res. 9:1741–1749. 2003.

28 

Wu G, Mannam AP, Wu J, Kirbis S, Shie JL, Chen C, Laham RJ, Sellke FW and Li J: Hypoxia induces myocyte-dependent COX-2 regulation in endothelial cells: role of VEGF. Am J Physiol Heart Circ Physiol. 285:2420–2429. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Wu G, Luo J, Rana JS, Laham R, Sellke FW and Li J: Involvement of COX-2 in VEGF-induced angiogenesis via P38 and JNK pathways in vascular endothelial cells. Cardiovasc Res. 69:512–519. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Zhang A, Meng L, Wang Q, Xi L, Chen G, Wang S, Zhou J, Lu Y and Ma D: Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2. Oncol Rep. 15:831–836. 2006.PubMed/NCBI

31 

Yao JS, Chen Y, Zhai W, Xu K, Young WL and Yang GY: Minocycline exerts multiple inhibitory effects on vascular endothelial growth factor-induced smooth muscle cell migration. Circ Res. 95:364–371. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Giatromanolaki A, Koukourakis MI, Kakolyris S, Turley H, O’Byrne K, Scott PA, Pezzella F, Georgoulias V, Harris AL and Gatter KC: Vascular endothelial growth factor, wild-type p53, and angiogenesis in early operable non-small cell lung cancer. Clin Cancer Res. 4:3017–3024. 1998.PubMed/NCBI

33 

Ambs S, Bennett WP, Merriam WG, Ogunfusika MO, Oser SM, Khan MA, Jones RT and Harris CC: Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53. Br J Cancer. 78:233–239. 1998. View Article : Google Scholar : PubMed/NCBI

34 

Cavazzola LT, Rosa AR, Schirmer CC, Gurski RR, Telles JP, Mielke F, Meurer L, Edelweiss MI and Kruel CD: Immunohistochemical evaluation for P53 and VEGF (Vascular Endothelial Growth Factor) is not prognostic for long term survival in end stage esophageal adenocarcinoma. Rev Col Bras Cir. 36:24–34. 2009. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Hu J, Chen C, Su Y, Du J, Qian X and Jin Y: Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells. Exp Ther Med 4: 1045-1050, 2012.
APA
Hu, J., Chen, C., Su, Y., Du, J., Qian, X., & Jin, Y. (2012). Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells. Experimental and Therapeutic Medicine, 4, 1045-1050. https://doi.org/10.3892/etm.2012.702
MLA
Hu, J., Chen, C., Su, Y., Du, J., Qian, X., Jin, Y."Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells". Experimental and Therapeutic Medicine 4.6 (2012): 1045-1050.
Chicago
Hu, J., Chen, C., Su, Y., Du, J., Qian, X., Jin, Y."Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells". Experimental and Therapeutic Medicine 4, no. 6 (2012): 1045-1050. https://doi.org/10.3892/etm.2012.702
Copy and paste a formatted citation
x
Spandidos Publications style
Hu J, Chen C, Su Y, Du J, Qian X and Jin Y: Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells. Exp Ther Med 4: 1045-1050, 2012.
APA
Hu, J., Chen, C., Su, Y., Du, J., Qian, X., & Jin, Y. (2012). Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells. Experimental and Therapeutic Medicine, 4, 1045-1050. https://doi.org/10.3892/etm.2012.702
MLA
Hu, J., Chen, C., Su, Y., Du, J., Qian, X., Jin, Y."Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells". Experimental and Therapeutic Medicine 4.6 (2012): 1045-1050.
Chicago
Hu, J., Chen, C., Su, Y., Du, J., Qian, X., Jin, Y."Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells". Experimental and Therapeutic Medicine 4, no. 6 (2012): 1045-1050. https://doi.org/10.3892/etm.2012.702
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