Original Article Overcoming Taxol resistance through the inhibition of EGFR-mediated glucose metabolism in oral cancer cells

Li-Min Liang, Lin Feng, Zhao-Gao Zhang, Bo Wei
2017 Int J Clin Exp Med   unpublished
Epidermal growth factor receptor (EGFR) is frequently expressed in many types of cancer including the oral squamous cell carcinoma (OSCC). As its overexpression is frequently associated with poor clinical outcome. Paclitaxel (Taxol) is a mitotic inhibitor used in cancer chemotherapy. However, although more and more patients accumulated resistance to Taxol, the mechanism remains unclear. The purpose of this study was to assess the novel glucose metabolism features in Taxol-resistant cells and
more » ... istant cells and whether there is a synergistic effect produced by incorporating Taxol (paclitaxel) with glycolysis inhibitors in the combined treatment of oral squamous cell carcinoma (OSCC). Methods: We studied two strains of cultured oral cancer cells, one with reduced EGFR expression (OECM-1 cells) and another with elevated EGFR expression (SAS cells). Results: Overexpression of EGFR in OECM-1 cells promoted glucose metabolism, while siRNA knockdown of EGFR in SAS cells inhibited glucose metabolism. Moreover, our data showed a strong correlation between glucose metabolism and Taxol resistance in oral cancer cells. Taxol resistant oral cancer cells displayed highly activated glucose metabolism. Finally, we reported a synergistic effect produced by incorporating Taxol (paclitaxel) with glycolysis inhibitors-2DG and 3BrPA in the combined treatment of oral squamous cell carcinoma in vitro and in vivo. Conclusion: Our data showed overexpression of EGFR contributed to Taxol resistance in oral cancer cells and the Taxol resistant cells obtained elevated EGFR expression levels. This study provides a novel perspective on the overcoming of chemo-resistant patients in clinical treatment.
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