Anti-tumor effects of lapatinib on HER2-positive canine prostatic carcinoma cell lines

Abstract

Background: Canine prostatic carcinoma (cPC) is a urogenital tumor with poor prognosis, for which no effective treatment has been established. Recently, it has been shown that human epidermal growth factor receptor type 2 (HER2) is overexpressed in cPC cells; however, the efficacy of HER2-targeted therapy remains unclear. Aim: Investigate the anti-tumor effect of lapatinib on HER2-positive cPC cell lines. Methods: Two cell lines (muPC and bePC) were established from two dogs with cPC and the effects of lapatinib treatment on cell proliferation, apoptosis, and HER2 downstream signaling were investigated. Furthermore, muPC was used to generate tumor-bearing mice, and the anti-tumor effects of lapatinib were examined in vivo. Results: Lapatinib treatment inhibited the proliferation and phosphorylation of Erk1/2 and Akt, which are downstream signals of HER2. Furthermore, the TUNEL assay showed that lapatinib induced apoptosis in both cell lines. The muPC-engrafted nude mouse model showed that lapatinib significantly inhibited tumor growth and increased the area of necrotic tumor tissue compared to the vehicle-treated groups. Conclusion: Lapatinib exerts anti-tumor effects on cPC cells by inhibiting HER-2 signaling.