Synergistic anti-tumor activity of cetuximab combining with cisplatin in human nasopharyngeal carcinoma cells

Abstract

Abstract: AIM: To detect the effect of cetuximab combining with cisplatin on growth effect of nasopharyngeal carcinoma xenografts in nude mice and its possible mechanism.METHODS: HONE1 cancer cells were suspended and injected into nude mice subcutaneouly.Then the mice were randomly assigned to four groups: normal saline group, cetuximab group, cisplatin group and combination group.The largest and smallest diameters of athymic mouse tumor were measured regularly, and the tumor volume was calculated.After treatment, all animals were sacrificed, the tumor xenografts were weighed and the inhibitory rates were calculated. The expression of phospho-protein kinase β (p-AKT) and phospho-extracellular signal regulated kinase (p-ERK) were detected with immunohistochemistry.RESULTS: The tumor volume and average weight of cetuximab group after treatment had no significant differentce, there was obvious inhibitory effect in cisplatin group and the combination with cetuximab group, but the later was more significant.The immunohistochemistry assay showed that the expression levels of p-AKT and p-ERK were higher in the samples from the group treated with cisplatin alone compared with saline group, but reduced when treated with cetuximab combined with cisplatin or not.CONCLUSION: The growth of transplantation tumor on HONE1 nasopharyngeal carcinoma bearing cancer in nude mice had no significant effect, it could enhance the antitumor effect of cisplatin on nasopharyngeal carcinoma xenografts.

Key words: nasopharyngeal carcinoma, epidermal growth factor receptor, cetuximab, cisplatin

CLC Number:

R965.1

LI Jing-jing, FENG Gong-li, ZHU Xiao-feng, ZHANG Xiao-shi. Synergistic anti-tumor activity of cetuximab combining with cisplatin in human nasopharyngeal carcinoma cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(7): 735-739.

References

[1] Ciardiello F, TortoraG. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor [J]. Clin Cancer Res, 2001, 7(10): 2958-2970.
[2] Steiner P, Joynes C, Bassi R, et al. Tumor growth inhibition with cetuximab and chemotherapy in non-small cell lung cancer xenografts expressing wild-type and mutated epidermal growth factor receptor[J]. Clin Cancer Res, 2007, 13(5): 1540-1551.
[3] Kim S, Prichard CN, Younes MN, et al. Cetuximab and irinotecan interact synergistically to inhibit the growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice[J]. Clin Cancer Res, 2006, 12(2): 600-607.
[4] Prewett M, Rothman M, Waksal H, et al. Mouse-human chimeric anti-epidermal growth factor receptor antibody C225 inhibits the growth of human renal cell carcinoma xenografts in nude mice[J]. Clin Cancer Res, 1998, 4 (12): 2957-2966.
[5] Teo PM, Kwan WH, Lee WY, et al. Prognosticators determining survival subsequent to distant metastasis from nasopharyngeal carcinoma[J]. Cancer, 1996, 77(12): 2423-2431.
[6] Leong JL, Loh KS, Putti TC, et al. Epidermal growth factor receptor in undifferentiated carcinoma of the nasopharynx[J]. Laryngoscope, 2004, 114(1): 153-157.
[7] Chua DT, Nicholls JM, Sham JS, et al. Prognostic value of epidermal growth factor receptor expression in patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy and radiotherapy[J]. Int J Radiat Oncol Biol Phys, 2004, 59(1): 11-20.
[8] Mai HQ, Zeng ZY, Zhang HZ, et al. Correlation of endothelin A receptor expression to prognosis of nasopharyngeal carcinoma[J]. Ai Zheng, 2005, 24(5): 611-615.
[9] Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic recurrent head and neck cancer: an Eastern Cooperative Oncology Group study[J]. J Clin Oncol, 2005, 23(34): 8646-8654.
[10] Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma[J]. J Clin Oncol, 2005, 23(15): 3568-3576.
[11] Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck[J]. N Engl J Med, 2006, 354(6): 567-578.
[12] Brozovic A, Osmak M. Activation of mitogen-activated protein kinases by cisplatin and their role in cisplatin-resistance[J]. Cancer Lett, 2007, 251(1): 11-16.
[13] Fraser M, Bai T, Tsang BK. AKT promotes cisplatin resistance in human ovarian cancer cells through inhibition of p53 phosphorylation and nuclear function[J]. Int J Cancer, 2008, 122(3): 534-546.
[14] Lee MW, Kim DS, Min NY, et al. AKT1 inhibition by RNA interference sensitizes human non-small cell lung cancer cells to cisplatin[J]. Int J Cancer, 2008, 122 (10): 2380-2384.
[15] DeHaan RD, Yazlovitskaya EM, Persons DL. Regulation of p53 target gene expression by cisplatin-induced extracellular signal-regulated kinase[J]. Cancer Chemother Pharmacol, 2001, 48(5): 383-388.
[16] Sung FL, Pang RT, Ma BB, et al. Pharmacoproteomics study of cetuximab in nasopharyngeal carcinoma[J]. J Proteome Res, 2006, 5(12): 3260-3267.