Thymoquinone affects hypoxia-inducible factor-1α expression in pancreatic cancer via HSP90 and PI3K/Akt/mTOR pathways

Abstract Purpose To clarify the therapeutic effects of thymoquinone (TQ) in pancreatic cancer (PC) and the potential hypoxia-inducible factor-1α (HIF-1α)-mediated mechanisms. Methods Western blotting and polymerase chain reaction were used to detect the expression levels of HIF-1α in PC cells treated with TQ. The effects of TQ on proliferation, migration, invasion, cell cycle, and apoptosis of PC cells and pancreatic ductal epithelial cells were assessed using in vitro experiments. Results TQ significantly inhibited the migration and invasion ability of PANC-1 cells (p < 0.05) but had no effects in hTERT-HPNE cells, and it significantly increased the proportion of the G2 phase and promoted apoptosis in PANC-1 cells compared with those in hTERT-HPNE cells (p < 0.05). Additionally, TQ significantly inhibited the expression of HIF-1α and phosphatidyl inositol-4,5-bisphosphate-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR)-related proteins in PANC-1 cells (p < 0.05). TQ affected the interaction between heat shock protein 90 (HSP90) and HIF-1α in PANC-1 cells. Conclusion TQ showed suppressive effects on proliferation, migration, invasion, cell cycle, and apoptosis of PC; promoted ubiquitination-mediated degradation of HIF-1α by affecting the interaction of HIF-1α with HSP90; and reduced HIF-1α synthesis by affecting PI3K/Akt/mTOR signaling pathway. The findings suggest that TQ might have potential anti-tumor effects in PC.