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Regulator of G‑protein signaling 5 (RGS5), a tissue‑specific signal‑regulating molecule, plays a key role in the development of the vasculature. It was recently found that RGS5 is abundantly expressed in epithelial ovarian cancer (EOC) compared with the normal ovaries. However, the distribution of RGS5 in EOC and its significance require further investigation. The aim of the present study was to investigate the expression of RGS5 in EOC, as well as its association with cancer differentiation, metastasis and clinicopathological parameters. Immunohistochemistry (IHC), western blotting, RT‑PCR, wound‑healing, cell proliferation and flow cytometric assays were the methods used in the present study. RGS5 was highly expressed in the cytoplasm of ovarian carcinoma cells and in microvascular structures. The expression of RGS5 in EOC was negatively associated with peritoneal metastasis (P=0.004), but it was not found to be associated with age, tumor size, clinical stage or lymph node metastasis (P>0.05). EOC patients with high RGS5 expression had a prolonged progression‑free survival (72.34±8.41 vs. 43.56±5.41 months, P<0.001). High expression of RGS5 was correlated with significantly lower microvascular density (MVD) as indicated by the expression of CD34, whereas the opposite was observed in tissues with low RGS5 expression (P<0.05). Hypoxia increased RGS5 expression in ovarian carcinoma‑derived endothelial cells (ODMECs), whereas the proliferative capacity of ODMECs exhibited a significant increase following RNAi‑mediated reduction of RGS5 expression. These data indicated that RGS5 plays a key role in angiogenesis in ovarian carcinoma. In addition, RGS5 downregulated the expression of the downstream proteins CDC25A, CDK2 and cyclin E, which are mediated by the mitogen‑activated protein kinase/extracellular signal‑regulated kinase pathway, causing ODMEC arrest in the G1 phase of the cell cycle under hypoxic conditions. Collectively, our data indicated that RGS5 is crucial for the occurrence and development of ovarian cancer, and that RGS5 and its signaling pathway may serve as anti‑angiogenesis targets for the treatment of ovarian cancer.

Aims: Fibroblast growth factor 21 (FGF21) is a powerful endocrine hormone modulating glucose and lipid metabolism and represents a promising drug for type 2 diabetes. The present study was to determine the effect of FGF21 on high glucose-induced damage and dysfunction in endothelial cells., Methods: The protein expression of β-klotho was examined in human umbilical vein endothelial cell (HUVECs) using immunofluorescence and Western blotting. HUVECs were cultured in medium with normal glucose (NG), high glucose (HG) and HG + FGF21 (30 nM). Cell viability, migration, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase, nitric oxide (NO) production, intracellular cyclic guanosine monophosphate (cGMP) and endothelial nitric oxide synthase (eNOS) phosphorylation at Ser-1177/Ser-633 sites were measured., Results: β-klotho, the anchor protein of FGF21, is expressed in HUVECs. Administration of FGF21 prevented HG-induced impairment of cell viability, migration, oxidant stress, NO production and intracellular cGMP levels in HUVECs. FGF21 also rescued HG-induced decrease of eNOS phosphorylation at Ser-1177 and Ser-633. HG and FGF21 had no effects on eNOS phosphorylation at Ser-617 and Thr-495. Inhibition of AMP-activated protein kinase (AMPK), but not Akt or Ca(2+)/calmodulin-dependent protein kinase II, abolished the protective effect of FGF21 on eNOS phosphorylation at Ser-1177. The protective effect of FGF21 on eNOS phosphorylation at Ser-633 was also abolished by inhibition of AMPK but not by Akt or cAMP-dependent protein kinase A., Conclusion: Our results provide the first evidence that FGF21 protects against high glucose induced cell damage and eNOS dysfunction in an AMPK-dependent manner in HUVECs, and suggest that FGF21 may be a promoting therapeutic agent for vascular complications in diabetes., (© 2014 S. Karger AG, Basel.)