Sunitinib induced resistance of endothelial cells by up-regulating P-glycoprotein and PI3K/Akt pathway

Drug resistance is a crucial obstacle to achieve satisfactory chemotherapeutic effects. Numerous studies have shown that the PI3K/Akt signaling pathway plays significant role in various processes of cellular events and tumor progression, while few focused on drug endothelial cells. The present study aims explore relationship anticancer drugs human microvessel cells (HMEC-1). We established stable sunitinib-resiatant (HMEC-su) after long-term exposure sunitinib (a small-molecule tyrosine kinase receptor inhibitor) for 12 months. HMEC-su showed alternations cell morphology exhibited 2.32-fold higher IC50 than parental HMEC-1 Expression P-glycoprotein (P-gp) breast cancer-resistance protein (ABCG2) which mediates efflux, increased significantly lines compared with by western blots assay. Our further demonstrates LY294002 (blocking pathway) enhances sensibility suntinib inhibits gene transcription expression P-gp, ABCG2 In conclusion, these results indicate could reverse P-gp mediated-drug inhibiting signaling.