Ovarian cancer is a lethal gynecologic tumor and is generally resistant to conventional treatments. Stable cancer-associated fibroblasts (CAFs) are important cellular components in the ovarian cancer tumor microenvironment and may provide novel resources for future treatment strategies. Different subtypes of CAFs display specific functions in tumor pathogenesis and various CAF markers suggest potential treatment targets, such as FAP and GPR77. Both autocrine and paracrine cytokines play important roles in the CAF activation process and regulate tumor progression. Downstream mediators and pathways, including IL-6, TGF-β, NF-κB, mitogen-activated protein kinase (MAPK), and AKT/mTOR/(p70S6K), play important roles in the initiation, proliferation, invasiveness, and metastasis of ovarian cancer cells and also participate in angiogenesis, therapeutic resistance, and other biological processes. Several clinical or preclinical trials have targeted stromal fibroblasts and focused on the properties of CAFs to enhance ovarian cancer treatment outcomes. This review concentrates on the origins, subtypes, and activation of CAFs, as well as specific roles of CAFs in regulating tumor development and drug resistance, and aims to provide potential and prospective targets for improving the therapeutic efficacy of ovarian cancer treatment.

The study was conducted to investigate the effect of Salvianolic acid B (Sal B) on TNF-α-stimulated adhesion molecule expression i.e. vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in human aortic endothelial cells (HAECs) under laminar shear stress (LSS) condition. Exposure of HAECs to LSS (12 dynes/cm² for 6 h decreased the TNF-α-induced protein expression of adhesion molecules i.e. VCAM-1, ICAM-1 and E-selectin. Pre-treatment of HAECs with Sal B (10 μg/ml) then exposed to LSS (12 dynes/cm²) for 6 h significantly inhibited VCAM-1, ICAM-1 and E-selectin expression stimulated by TNF-α. Moreover, combined Sal B and LSS treatment inhibited the adhesiveness of monocytic U937 cells to TNF-α-stimulated HAECs. We further examined the molecular mechanisms and found that the combination of Sal B and LSS treatment dramatically inhibited TNF-α-induced NF-κB activation evidenced by IκBα degradation and p65 nuclear translocation in HAECs. This study provides the first biomechanopharmacological evidence that Sal B has a combination effect with LSS to reduce the expression of three adhesion molecules, leading to reduced monocyte adhesion to HAECs, at least in part, by inhibiting the NF-κB signaling pathway. Data from this study thus support the potential clinical application of Sal B in vascular inflammatory diseases.