Hypoxia activates PSCs to promote the progression of pancreatic cancer / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the effects of hypoxia on the activation of pancreatic stellate cells (PSCs) and progression of pancreatic cancer. Methods:In the present study, PSCs were cultured under normoxic or hypoxic conditions or co-cultured with pancreatic cancer cell line Panc-1. Then, the shRNA of HIF-1α was stably transfected into PSC cells. Activation of PSCs was detected by immunofluorescence. Secretions of IL-6, SDF-1 and VEGF-A in PSCs were determined by ELISA assay. Invasion of Panc-1 was detected by the Transwell assay. The proteins of E-cadherin and Vimentin in Panc-1 cells were determined by Western blot. Results: Hypoxia activated PSCs and significantly increased IL-6, SDF-1 and VEGF-A secretion in PSCs. Moreover, hypoxia significantly upregulated the PSCs-induced invasion of Panc-1 cells, increased the protein expressions of HIF-1α and Vimentin, and decreased the protein expression of E-cadherin. Furthermore, knockdown of HIF-1α obviously abrogated hypoxia-induced PSC activation and IL-6, SDF-1 and VEGF-A secretion in PSCs, and abolished hypoxia-enhanced epithelial-mesenchymal transition and invasion of Panc-1 cells. Conclusion: Hypoxia enhances the epithelial-mesenchymal transition and invasion of PSCs and strengthens HIF-1α expression via activating PSCs.