Knockdown ofSERPINE1reverses resistance of triple-negative breast cancer to paclitaxel via suppression ofVEGFA

Breast cancer (BC) has a poor prognosis and a high number of visceral metastases. Serine protease inhibitor, clade E member 1 (SERPINE1) is a molecule involved in several human malignancies. However, it remains unknown ifSERPINE1plays a role in the development of taxane resistance in TNBC cells. In the present study, the role and mechanism ofSERPINE1in the development of paclitaxel (PTX) resistance in TNBC cells were investigated. A bioinformatics analysis of gene expression profiles in PTX-resistant cells indicated thatSERPINE1was significantly associated with PTX resistance. Furthermore, the levels ofSERPINE1mRNA and protein were higher in PTX-resistant cells with respect to those in PTX-sensitive parent cells. Knockdown ofSERPINE1significantly inhibited cell survival and induced cell apoptosisin vitro. In addition,SERPINE1silencing led to downregulation of the key angiogenetic vascular endothelial growth factor A (VEGFA). Furthermore, suppression ofSERPINE1markedly attenuated tumor growthin vivo. Collectively, these findings indicated thatSERPINE1significantly contributed to the proliferation and apoptosis of TNBC cells by regulatingVEGFAexpression. The present study demonstratedSERPINE1as an oncogene in PTX drug resistance of breast cancer, and revealed that it may serve as a possible target for treating BC.