Curcumin Improves Chemotherapy Resistance in Breast Cancer Cells via Inhibiting the Secretion of FGF2/FGFR2 from Cancer-Associated Fibroblasts

Abstract

Background: Curcumin is an active ingredient isolated from the turmeric with anti-tumor activity. Cancer-associated fibroblasts (CAFs) can promote the development of chemical resistance in tumor cells. The present study aimed to explore the effect and molecular mechanism of curcumin on the chemosensitivity of breast cancer (BC). Methods: BC cell lines (MCF-7 and MDA-231) and paclitaxel (PTX)-resistant cell lines (MCF-7/PTX and MDA-231/PTX) were initially subjected to treatment with either curcumin or PTX. The cell proliferation and apoptosis rates were subsequently evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry. Western blotting was employed to evaluate the protein expression of fibroblast growth factor 2 (FGF2) and specific receptor-FGF receptor 2 (FGFR2). Because of the involvement of certain factors secreted by CAFs in chemotherapy resistance, the BC cells were exposed to a conditioned medium derived from CAFs (CAFs-CM). Subsequently, the changes in PTX resistance were monitored following interventions with both CAFs-CM and curcumin. Results: Curcumin blocked the proliferation (p < 0.01) and promoted apoptosis in BC cells (p < 0.01). Moreover, it reduced the proliferation (p < 0.01) and augmented the apoptosis (p < 0.01) in MCF-7/PTX and MDA-231/PTX cells after PTX intervention by inhibiting the expression of FGF2 and FGFR2. CAFs-CM enhanced PTX resistance in BC cells, while the phenomenon was reversed by curcumin. Moreover, CAFs-CM induced an increase in FGF2 and FGFR2 protein expression in BC cells (p < 0.01), and this effect was eliminated after curcumin treatment (p < 0.01). Conclusions: Curcumin increases BC cell sensitivity to PTX by inhibiting the secretion of FGF2/FGFR2 from CAFs.