Tek bir ajan olarak setuksimab oral kavite kanser hücrelerinde doza bağımlı etkiye sahiptir: Bir in vitro çalışma

Abstract

Objective: To evaluate the antitumor effect of cetuximab as a single agent for the treatment of oral cavity cancers and to clarify the dosedependent growth inhibitory effect in oral cavity squamous cell carcinoma cell line (OCSCCCL).
Methods: The OCSCCCL (UPCI-SCC131) were cultured and continuously monitored using the xCELLigence RTCA SP instrument. Thereafter, they were divided into seven groups as: (i) negative control: medium+OCSCCCL, (ii) positive control: medium+OCSCCCL+cisplatin 10 μM/ml, (iii) medium+OCSCCCL+cetuximab 25 μg/ml, (iv) medium+OCSCCCL+cetuximab 50 μg/ml, (v) medium+OCSCCCL+cetuximab 100 μg/ml, (vi) medium+OCSCCCL+cetuximab 200 μg/ml, (vii) medium+OCSCCCL+cetuximab 400 μg/ml. The cell index and viability were statistically analyzed and compared between groups.
Results: The distribution of cell index (mean value) and percentage of viability in groups were as follows: (i) 2.66 (100%), (ii) 0.17 (6.08%), (iii) 2.28 (85.71%), (iv) 2.31 (86.84%), (v) 1.92 (72.18%), (vi) 1.79 (67.29%), (vii) 0.28 (10.53%). The change trend in drug concentration was statistically different in all study groups to which cetuximab was administered (Pillai’s trace; p<0.0001). The antitumor effect of cetuximab was initially detected at a dose of 100 μg/mL, when compared with negative control (p=0.01). However, a dose of 400 μg/mL was required in order to have a statistically similar antitumor
effect of cisplatin at a dose of 10 μM.
Conclusion: Cetuximab alone is a potentially effective chemotherapeutic agent and has a concentration-dependent growth inhibitory effect in OCSCCCL. The antitumor activity of cetuximab was initially detected at a dose of 100 μg/mL. However, significant antitumor effect was determined at a dose of 400 μg/mL.

Keywords

• Antitümöral etki,setuksimab,oral kavite,karsinom,Antitumor,cetuximab,oral cavity,cancer

References

1. 1. Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 2004;59(2 Suppl):21–6.
2. 2. Warburton D, Zhao J, Berberich MA, Bernfield M. Molecular embryology of the lung: then, now, and in the future. Am J Physiol 1999;276:L697–704.
3. 3. Lovicu FJ, McAvoy JW. Growth factor regulation of lens development. Dev Biol 2005;280:1–14.
4. 4. Hardy KM, Booth BW, Hendrix MJ, Salomon DS, Strizzi L. ErbB/EGF signaling and EMT in mammary development and breast cancer. J Mammary Gland Biol Neoplasia 2010;15:191–9.
5. 5. Schneider MR, Wolf E. The epidermal growth factor receptor ligands at a glance. J Cell Physiol 2009;218:460–6.
6. 6. Normanno N, De Luca A, Bianco C, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006;366:2–16.
7. 7. Sharafinski ME, Ferris RL, Ferrone S, Grandis JR. Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck. Head Neck 2010;32:1412–21.
8. 8. Okamoto I. Epidermal growth factor receptor in relation to tumor development: EGFR-targeted anticancer therapy. FEBS J 2010; 277:309–15.

9. 9. Ciardiello F, Tortora G. EGFR antagonist in cancer treatment. N Engl J Med 2008;358:1160–74.
10. 10. Schmitz KR, Ferguson KM. Interaction of antibodies with ErbB receptor extracellular regions. Exp Cell Res 2009;315:659–70.
11. 11. Bou-Assaly W, Mekherji S. Cetuximab (erbitux). AJNR Am J Neuroradiol 2010;31:626–7.
12. 12. Hadari YR, Doody JF, Wang Y, et al. The IgG1 monoclonal antibody cetuximab induces degradation of the epidermal growth factor receptor. Presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, San Francisco, CA, January 22–24, 2004 (abstr 234).
13. 13. Harding J, Burtness B. Cetuximab: an epidermal growth factor receptor chimeric human-murine monoclonal antibody. Drugs Today (Barc) 2005;41:107–27.
14. 14. Baselga J, Pfister D, Cooper MR, et al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol 2000;18:904–14.
15. 15. Shin DM, Donato NJ, Perez-Soler R, et al. Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res 2001;7:1204–13.
16. 16. Raben D, Helfrich B, Chan DC, et al. The effects of cetuximab alone and in combination with radiation and /or chemotherapy in lung cancer. Clin Cancer Res 2005;11:795–805.
17. 17. Sung FL, Poon TCW, Hui EP, et al. Antitumor effect and enhancement of cytotoxic drug activity by cetuximab in nasopharyngeal carcinoma cells. In Vivo 2005;19:237–46.
18. 18. Zhang N, Erjala K, Kulmala J, et al. Concurrent cetuximab, cisplatin, and radiation for squamous cell carcinoma of the head and neck in vitro. Radiother Oncol 2009;92:388–92.
19. 19. Bussu F, Pozzoli G, Giglia V, et al. Effects of administration of epidermal growth factor receptor specific inhibitor cetuximab, alone and in combination with cisplatin, on proliferation and apoptosis of Hep-2 laryngeal cancer. J Laryngol Otol 2014;128:902–8.