Combined effects of EGFR and hedgehog signaling blockade on inhibition of head and neck squamous cell carcinoma

Int J Clin Exp Pathol. 2017 Sep 1;10(9):9816-9828. eCollection 2017.

Abstract

Head and neck cancer, the sixth most common cancer, has poor prognosis and short survival. Anti-epidermal growth factor receptor (EGFR) therapies have been recently developed for the treatment of multiple cancer types. JK184, an inhibitor of Hedgehog pathway, prevents the growth of many tumor cell lines in several studies. Whether it enhances chemosensitivity to block EGFR expression by shEGFR plasmid and blocks the Hedgehog pathway by JK184 remains unclear in sinonasal tumors. The changes in cell apoptosis and proteins have been detected by flow cytometry and Western blotting, respectively. In vivo, the maxillary sinus model was established to detect the inhibition of tumor growth and tumor weight. A synergistic effect has been observed with JK184 combined with shEGFR, which is positively correlated with increased autophagy. The maxillary sinus model results demonstrated that the inhibitory rate of the combined therapy was higher than that of JK184 or shEGFR alone. Our findings suggest that JK184 in combination with shEGFR might have potential as a new therapeutic regimen against sinonasal tumors.

Keywords: EGFR; Hedgehog; Malignant sinonasal tumors; apoptosis; autophagy.