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DOI: 10.1055/s-0043-1767251
Investigation of Cetuximab Pretreatment Effects on Cisplatin or Sunitinib Cytotoxicity in Head and Neck Carcinoma Cells in vitro.
Introduction Chemotherapy is a known treatment option for head and neck carcinomas. Cisplatin is used as monotherapy or in combination with cetuximab in aggressive cases while sunitinib has shown effective alone or in combination with cetuximab. Although these agents exert their effect through membrane drug transporters, the molecular mechanism behind cetuximab’s effect on cisplatin and sunitinib cytotoxicity in treating head and neck cancer is unclear. In vitro models of head and neck carcinoma and normal oral epithelium are used to explore these pharmacological ambiguities.
Methods Drug transport activities in cetuximab pretreated cells were explored using the fluorescent substrates 4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide, Hoechst 33342, and calcein-AM with and without inhibition. The analysis of drug transporters’ expression was achieved by qPCR and immunofluorescence. PrestoBlue viability assay was used to determine cytotoxicity of cisplatin and sunitinib in cetuximab pretreated cells. Results: Drug transport activity was detected in all analyzed cells. In cancer cells pretreated with cetuximab, the expression of transporters related to drug resistance was downregulated compared to nontumor cells where the expression was unaltered. In addition, the half maximal effective toxic concentration for cisplatin and sunitinib decreased by 0.75- and 0.82-fold respectively whereas nontumor cells were insensitive to treatments.
Conclusion The expression and activity of drug transporters vital in conferring drug resistance properties to head and neck cancer cells are regulated by cetuximab. Cisplatin and sunitinib cytotoxicity are enhanced through this deregulation potentiating the effect of these drugs on head and neck cancer cells.
Publication History
Article published online:
12 May 2023
Georg Thieme Verlag
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