Cancer-associated fibroblasts affect breast cancer cell sensitivity to chemotherapeutic agents by regulating NRBP2

Abstract

Objective To uncover the role of nuclear receptor-binding protein 2 (NRBP2) in cancer-associated fibroblasts (CAFs), and CAFmediated TAM sensitivity in breast cancer (BC). Methods 10 pairs of matched tumor tissues and adjacent normal tissues were collected and CAFs and normal fibroblasts (NFs) were isolated. CCK-8 as well as colony formation assays showed the effects on cell growth. qPCR and Immunoblot showed the expression of NRBP2 in CAFs. FCM as well as Immunoblot assays exhibited the effects on cell apoptosis. Immunoblot further confirmed the mechanism. Results CAFs contributed to BC cell growth. In addition, the expression of NRBP2 is downregulated in CAFs. NRBP2 suppressed CAF-induced resistance in BC cells. Further, NRBP2 expression in CAF group increased TAM induced apoptosis. Mechanically, NRBP2 in CAFs inhibited Akt pathway, therefore suppressed resistance in BC cells. Conclusion CAFs affected BC cell sensitivity to TAM by regulating NRBP2.