Celecoxib attenuates cachectic events in mice by modulating the expression of vascular endothelial growth factor

Xu,Xiaoya; Jiang,Man; Zhang,Ying; Bi,Yuli; Han,Mingyong

doi:10.3892/mmr.2014.2730

Celecoxib attenuates cachectic events in mice by modulating the expression of vascular endothelial growth factor

Authors:
- Xiaoya Xu
- Man Jiang
- Ying Zhang
- Yuli Bi
- Mingyong Han
View Affiliations

Affiliations: Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: October 21, 2014 https://doi.org/10.3892/mmr.2014.2730
Pages: 289-294

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chronic inflammation is one of the main symptoms of cancer cachexia, and cyclooxygenase 2 inhibitors, such as celecoxib, may be beneficial in counteracting the major symptoms of this syndrome. In the current study, celecoxib was orally administered to BALB/c male mice with colon 26 adenocarcinoma. Tumor growth, survival rate, body weight and food intake of the mice with cancer cachexia were recorded during the experiments. The host inflammatory response was assessed by morphological observations and hematoxylin‑eosin staining. The serum levels of vascular endothelial growth factor (VEGF), granulocyte‑macrophage colony‑stimulating factor, interleukin‑6 and tumor necrosis factor‑α in mice with cancer cachexia were measured by ELISA. Celecoxib administration attenuated the decline in body weight and food intake of mice with cancer cachexia, and improved the survival rate of cachectic mice. Erythrocyte counts and hemoglobin concentration significantly increased in cachectic mice receiving celecoxib compared with control cachectic mice. Notably, celecoxib administration significantly reduced the serum level of VEGF in mice with colon 26 adenocarcinoma, and the cachectic events were also relieved by treatment with a VEGF antibody. The cyclooxygenase 2 inhibitor celecoxib produced positive therapeutic effects in mice with cancer cachexia. This function was regulated at least partly by downregulation of serum levels of VEGF.

View Figures

View References

1	Fearon K, Strasser F, Anker SD, et al: Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 12:489–495. 2011. View Article : Google Scholar : PubMed/NCBI
2	Kumar NB, Kazi A, Smith T, et al: Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment. Curr Treat Options Oncol. 11:107–117. 2010. View Article : Google Scholar : PubMed/NCBI
3	Donohoe CL, Ryan AM and Reynolds JV: Cancer cachexia: mechanisms and clinical implications. Gastroenterol Res Pract. 2011:6014342011. View Article : Google Scholar : PubMed/NCBI
4	Argilés JM, Busquets S, Toledo M and López-Soriano FJ: The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care. 3:263–268. 2009.
5	Gupta SC, Kim JH, Kannappan R, et al: Role of nuclear factor κB-mediated inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents. Exp Biol Med (Maywood). 236:658–671. 2011.
6	Clària J: Publication of a special issue: resolution of acute inflammation and the role of lipid mediators. Scientific World Journal. 10:1553–1555. 2010.PubMed/NCBI
7	Tan BH, Ross JA, Kaasa S, et al: European Palliative Care Research Collaborative: Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review. J Genet. 90:165–177. 2011. View Article : Google Scholar
8	Argilés JM, Busquets S and López-Soriano FJ: Anti-inflammatory therapies in cancer cachexia. Eur J Pharmacol. 668(Suppl 1): S81–S86. 2011.
9	Batista ML Jr, Peres SB, McDonald ME, et al: Adipose tissue inflammation and cancer cachexia: possible role of nuclear transcription factors. Cytokine. 57:9–16. 2012. View Article : Google Scholar : PubMed/NCBI
10	Thiel A, Mrena J and Ristimäki A: Cyclooxygenase-2 and gastric cancer. Cancer Metastasis Rev. 30:387–395. 2011. View Article : Google Scholar
11	Turk HM, Camci C, Sevinc A, et al: Cyclooxygenase-2 expression is not a marker of poor survival in lung cancer. Asian Pac J Cancer Prev. 13:315–318. 2012. View Article : Google Scholar : PubMed/NCBI
12	Williams CS, Mann M and DuBois RN: The role of cyclooxygenases in inflammation, cancer and development. Oncogene. 18:7908–7916. 1999. View Article : Google Scholar : PubMed/NCBI
13	Morita Y, Hata K, Nakanishi M, et al: Cyclooxygenase-2 promotes tumor lymphangiogenesis and lymph node metastasis in oral squamous cell carcinoma. Int J Oncol. 41:885–892. 2012.PubMed/NCBI
14	Xin X, Majumder M, Girish GV, et al: Targeting COX-2 and EP4 to control tumor growth, angiogenesis, lymphangiogenesis and metastasis to the lungs and lymph nodes in a breast cancer model. Lab Invest. 92:1115–1128. 2012. View Article : Google Scholar : PubMed/NCBI
15	Tisdale MJ: Cachexia in cancer patients. Nat Rev Cancer. 2:862–871. 2002. View Article : Google Scholar
16	Davis TW, Zweifel BS, O’Neal JM, et al: Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting. J Pharmacol Exp Ther. 308:929–934. 2004. View Article : Google Scholar : PubMed/NCBI
17	Yang SY, Yu H, Krygier JE, Wooley PH and Mott MP: High VEGF with rapid growth and early metastasis in mouse osteosarcoma model. Sarcoma. 2007:956282007.PubMed/NCBI
18	Evans WJ, Morley JE, Argilés J, et al: Cachexia: a new definition. Clin Nutr. 27:793–799. 2008. View Article : Google Scholar : PubMed/NCBI
19	Serhan CN, Krishnamoorthy S, Recchiuti A and Chiang N: Novel anti-inflammatory - pro-resolving mediators and their receptors. Curr Top Med Chem. 11:629–647. 2011. View Article : Google Scholar : PubMed/NCBI
20	Zhao QT, Yue SQ, Cui Z, et al: Potential involvement of the cyclooxygenase-2 pathway in hepatocellular carcinoma-associated angiogenesis. Life Sci. 80:484–492. 2007. View Article : Google Scholar : PubMed/NCBI
21	Seelaender M, Batista M Jr, Lira F, Silverio R and Rossi-Fanelli F: Inflammation in cancer cachexia: to resolve or not to resolve (is that the question?). Clin Nutr. 31:562–566. 2012. View Article : Google Scholar : PubMed/NCBI
22	Argilés JM, López-Soriano FJ and Busquets S: Mechanisms to explain wasting of muscle and fat in cancer cachexia. Curr Opin Support Palliat Care. 1:293–298. 2007.PubMed/NCBI
23	Lawrence T and Fong C: The resolution of inflammation: anti-inflammatory roles for NF-kappaB. Int J Biochem Cell Biol. 42:519–523. 2010. View Article : Google Scholar : PubMed/NCBI
24	Patra SK and Arora S: Integrative role of neuropeptides and cytokines in cancer anorexia-cachexia syndrome. Clin Chim Acta. 413:1025–1034. 2012. View Article : Google Scholar : PubMed/NCBI
25	Laviano A, Molfino A, Seelaender M, et al: Carnitine administration reduces cytokine levels, improves food intake, and ameliorates body composition in tumor-bearing rats. Cancer Invest. 29:696–700. 2011. View Article : Google Scholar : PubMed/NCBI
26	Weidle UH, Klostermann S, Eggle D and Krüger A: Interleukin 6/interleukin 6 receptor interaction and its role as a therapeutic target for treatment of cachexia and cancer. Cancer Genomics Proteomics. 7:287–302. 2010.PubMed/NCBI
27	Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI
28	Shojaei F and Ferrara N: Antiangiogenesis to treat cancer and intraocular neovascular disorders. Lab Invest. 87:227–230. 2007. View Article : Google Scholar : PubMed/NCBI
29	Krzystek-Korpacka M, Matusiewicz M, Diakowska D, et al: Acute-phase response proteins are related to cachexia and accelerated angiogenesis in gastroesophageal cancers. Clin Chem Lab Med. 46:359–364. 2008. View Article : Google Scholar : PubMed/NCBI
30	Kemik O, Sumer A, Kemik AS, et al: The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer. World J Surg Oncol. 8:852010. View Article : Google Scholar : PubMed/NCBI
31	Valcárcel M, Mendoza L, Hernández JJ, et al: Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2. J Transl Med. 9:1422011.PubMed/NCBI
32	Kim YY, Lee EJ, Kim YK, et al: Anti-cancer effects of celecoxib in head and neck carcinoma. Mol Cells. 29:185–194. 2010. View Article : Google Scholar : PubMed/NCBI