Juglone down-regulates the Akt-HIF-1α and VEGF signaling pathways and inhibits angiogenesis in MIA Paca-2 pancreatic cancer in vitro

Abstract

Hypoxia-inducible factor -1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated Akt (p-Akt) are critical in pancreatic cancer cell growth, angiogenesis and metastasis. The ability of MIA Paca-2 pancreatic cancer cells to migrate and invade after treatment with juglone (5 hydroxy-1, 4-naphthoquinone) was analyzed by a transwell invasion and migration assay, a wound healing assay, and an in vitro tube formation assay using human umbilical vein endothelial cells (HUVEC). ELISA was used to determine the levels of HIF1-α. Western blot analysis was used to determine the level of VEGF, p-Akt, and carbonic anhydrase IX expression. Juglone down-regulated the expression of HIF-1α, VEGF, and significantly suppressed the phosphorylation of Akt. Juglone dose-dependently inhibited the metastatic potential of pancreatic cancer cells by inhibiting cell migration, invasion and wound healing assays. Juglone attenuated the aggressiveness of pancreatic cancer cells in vitro.