International Journal of Hematology-Oncology and Stem Cell Research 2018. 12(2):136-141.

Bevacizumab Inhibits Angiogenic Cytokines in Head and Neck Squamous Cell Carcinoma: From Gene to the Protein
Hossein Heydar, Kamran Mansouri, Maryam Norooznezhad, Fatemeh Norooznezhad, Abdolreza Mohamadnia, Naghmeh Bahrami

Abstract


Background: Head and neck squamous cell carcinoma (HNSCC) is one most prevalent cancers among worldwide. Aim of this study was to evaluate possible effect of bevacizumab, a vascular endothelial growth (VEGF) factor monoclonal antibody on HNSCC cells in vitro to evaluate angiogenic profile changes.

Materials and Methods: HNSCC cells were grown and after that different concentrations of bevacizumab were added in order to evaluate cytotoxic concentration using MTT assay. Then after, the cultured cells in presence of different concentration of bevacizumab were evaluated for gene expression of VEGF, matrix metalloprotease-2 (MMP-2) and MMP-9 using real time polymerase chain reaction (PCR). Moreover, the VEGF expression was evaluated by enzyme-linked immunosorbent assay (ELISA).

Results: The concentration at which half cells died (IC59) was calculated 1779 µg/mL and at this concentration, VEGF protein secretion was decreased by over one fold. RT-PCR results showed that MMP2, MMP9 and VEGF decreased by 1, 0.6 and 1.1 folds, respectively.

Conclusion: It seems that bevacizumab could be considered as a side therapy for patients with HNSCC due to its potential for inhibition of angiogenic related factors, but further complementary studies are necessary.

 


Keywords


Head and neck squamous cell carcinoma, Bevacizumab, Angiogenesis, Vascular endothelial growth, Matrix metalloproteases

Full Text:

PDF

References


Wilken R, Veena MS, Wang MB, et al. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011; 10:12.

Argiris A, Kotsakis A, Hoang T, et al. Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2013; 24(1):220-5.

Folkman J. Tumor angiogenesis: therapeutic implications. New Engl J Med. 1971; 285(21):1182-6.

Norooznezhad AH, Norooznezhad F, Ahmadi K. Next target of tranilast: inhibition of corneal neovascularization. Med Hypotheses. 2014; 82(6):700-2.

Ferrara N, Hillan KJ, Novotny W. Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun. 2005; 333(2):328-35.

Keshavarz M, Norooznezhad AH, Mansouri K, et al. Cannabinoid (JWH-133) therapy could be effective for treatment of corneal neovascularization. Iran J Med Hypotheses Ideas.2010; 4:3.

Norooznezhad AH, Norooznezhad F. Cannabinoids: Possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation. Med Hypotheses. 2017; 99:15-18.

Norooznezhad AH, Norooznezhad F, Bagheri N. Cannabinoids as Treatment for Hemophilic Arthropathy: Hypothesized Molecular Pathways. J Rep Pharm Sci. 2016; 5(2):89-93.

Ferrara N, Hillan KJ, Gerber H-P, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004; 3(5):391-400.

Wang Y, Fei D, Vanderlaan M, et al. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis. 2004; 7(4):335-45.

Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42.

Monk BJ, Sill MW, Burger RA, et al. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009; 27(7):1069-74.

Fujita K, Sano D, Kimura M, et al. Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma. Oncol Rep. 2007; 18(1):47-51.

Pluda JM. Tumor-associated angiogenesis: mechanisms, clinical implications, and therapeutic strategies. Semin Oncol. 1997; 24(2):203-218.

Nguyen A, Hoang V, Laquer V, et al. Angiogenesis in cutaneous disease: part I. J Am Acad Dermatol; 2009.61(6):921-42.

Roskoski R. Vascular endothelial growth factor (VEGF) and VEGF receptor inhibitors in the treatment of renal cell carcinomas. Pharmacol Res.2017; 120:116-132.

Minion LE, Tewari KS. The safety and efficacy of bevacizumab in the treatment of patients with recurrent or metastatic cervical cancer. Expert Rev Anticancer Ther. 2017; 17(3):191-198.

Boehm T, Folkman J, Browder T, et al. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature. 1997; 390(6658):404-7.

Rebucci M, Peixoto P, Dewitte A, et al. Mechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance. Int J Oncol. 2011; 38(1):189-200.

Nyflot MJ, Kruser TJ, Traynor AM, et al. Phase 1 trial of bevacizumab with concurrent chemoradiation therapy for squamous cell carcinoma of the head and neck with exploratory functional imaging of tumor hypoxia, proliferation, and perfusion. Int J Radiat Oncol Biol Phys. 2015; 91(5):942-51

Shih T, Lindley C. Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther. 2006; 28(11):1779-802.

Lin Z, Zhang Q, Luo W. Angiogenesis inhibitors as therapeutic agents in cancer: challenges and future directions. Eur J Pharmacol. 2016; 793:76-81

Byrne AM, Bouchier‐Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med. 2005; 9(4):777-94.

Rodrigues M, Xin X, Jee K, et al. VEGF secreted by hypoxic Müller cells induces MMP-2 expression and activity in endothelial cells to promote retinal neovascularization in proliferative diabetic retinopathy. Diabetes; 2013.62(11):3863-73.

Norooznezhad AH, Norooznezhad F. How could cannabinoids be effective in multiple evanescent white dot syndrome? A hypothesis. J Rep Pharm Sci. 2016; 5(1):41-44.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.