The Synergistic Effects of Pyrotinib and SHR-1316 on HER2-positve breast cancer

Abstract PYR was a new generation of HER-2 small molecule tyrosine kinase inhibitor, which inhibited a variety of HER family receptors. And SHR-1316 was one of the most popular drugs in the field of cancer therapy recently. The purpose of this study was to ascertain the effects of PYR combined with SHR-1316 and further explore its potential mechanism on HER2-positive BC. MTT assay, Wound-healing assay, and Transwell assay were used to detect the effects of PYR and SHR-1316 on the proliferation, migration, and invasion of HER2-positive BC cells. Cell apoptosis was tested through flow cytometry. Xenograft model was established to illustrate the synergistic effects of pyrotinib combined with SHR-1316 in vivo. Immunohistochemistry (IHC) was utilized to assess the expression of T cells in the SK-BR-3 tumor issue. Western blotting was performed to determine the expression of PD-L1, PI3K, p-PI3K, AKT, p-AKT, and FOXO1. The results showed that PYR and SHR-1316 had synergistic inhibited effects on the cell proliferation, migration, invasion of HER2-positive BC cells. PYR and SHR-1316 promoted synergistically BC cell apoptosis. PYR and SHR-1316 downregulated the expression of PD-L1, p-PI3K, p-AKT and upregulated the expression FOXO1. In the nude-mice Xenograft model, pyrotinib and SHR-1316 had synergistic inhibition effects on tumor growth.