The anti-angiogenic effect of dexamethasone in a murine hepatocellular carcinoma model by augmentation of gluconeogenesis pathway in malignant cells

Authors:
Publisher website
Google Scholar
Abstract
Purpose Angiogenesis is a long-term complex process involving various protein factors in hepatocellular carcinoma (HCC). Dexamethasone (Dex), considered as a synthetic glucocorticoid drug in clinical therapy, has been reported to have the therapeutic efficacy against liver cancer by intervention of abnormal glycolysis. In this study, we investigated the anti-angiogenic effect of Dex in murine liver cancer and attempted to demonstrate the potential mechanism. Methods The malignant cells H22 were treated with Dex. Western blotting was used to explore the expression of PEPCK and G6Pase which were the two key enzymes that regulated gluconeogenesis. The supernatants from cultured H22 treated by Dex were collected and co-cultured with HUVECs. In vitro, migration assay, transwell assay and tube formation assay were performed to assess for migration, proliferation and tube formation abilities of HUVECs, respectively. In situ murine hepatoma model with green fluorescent protein markers (HepG2-GFP) was constructed to determine angiogenesis after treatment by Dex. Results PEPCK and G6Pase were almost deficient in H22 compared with normal liver cells NCTC-1469 (P < 0.01). After treated by Dex, the gluconeogenesis could be restored significantly (P < 0.01) in H22 cells. The supernatant of H22 treated by Dex inhibited the migration, tube formation and endothelial permeability in HUVECs (P < 0.05). In mouse tissue, PEPCK and G6Pase were highly expressed in Dex group than control groups (P < 0.01). 11β-HSDs abnormally expressed in tumor also could be restored by Dex. Meanwhile, the density and total length of microvessels in Dex-treated group were less than those in HCC groups (P < 0.05). Conclusions This study explored the therapeutic efficacy of Dex in murine HCC. Dex might inhibit tumor growth and angiogenesis by augmenting the gluconeogenesis pathway.
Funding Information
  • Innovation Fund of CAMS & PUMC (NO. 1012014X06)

This publication has 37 references indexed in Scilit: