Anti-tumor Efficacy and Potential Mechanism of Pyrotinib in Locally Advanced Oral Squamous Cell Carcinoma

Abstract

Abstract Background The resistance to epidermal growth factor receptor (EGFR) target therapy is common in advanced oral squamous cell carcinoma (OSCC). Meanwhile human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to EGFR target treatment. However, the expression status and the clinical significance of HER2 in OSCC is still controversial. Pyrotinib has shown promising activity as a novel EGFR/HER2 dual inhibitor, in many advanced cancers, but its efficacy in OSCC has not been determined. Methods 57 locally advanced de novo OSCC patients admitted into a single tertiary referral hospital were enrolled in this study with the approval of the ethics committee. Through tissue microarray analysis of the primary tumors and paired para-tumor oral mucosa, the relationship between the expression levels of HER2 and the prognosis of OSCC patients had been investigated. To complement these findings, the antitumor efficacy of pyrotinib in OSCC was retrieved in vitro and in vivo. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of pyrotinib. Results This study revealed the primary tumor of OSCC had higher HER2 expression levels. Through Kaplan-Meier analysis, OSCC patients with high HER2 expression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, pyrotinib suppressed the proliferation, colony formation and migration of OSCC cells. Pyrotinib also promoted apoptosis of OSCC cells and induced cell cycle arrest. This study also confirmed that pyrotinib was able to inhibit the occurrence and development of OSCC effectively in vivo. Furthermore, western blotting revealed that pyrotinib suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK in vitro and in vivo. Conclusions This is the first study to exhibit the anti-OSCC effects of pyrotinib in vitro and in vivo, and demonstrated pyrotinib inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.