Abstract
Background Albendazole, a clinical antiparasitic drug, has been shown to have antitumor activity and supress expression of hypoxia-inducible factor 1-alpha. While hypoxia, the most prominent feature of tumor microenvironment, is associated with radiotherapy tolerance. Herein, we aimed to identify Albendazole as a candidates that improves tumor microenvironment and enhances the radiosensitivity of human pancreatic cancer cells. Methods MTT assay, clone formation and flow cytometry were performed to assess the effect of ABZ and radiation on PC cell line proliferation and apoptosis induction. In addition, the expression levels of hypoxia-inducible factor 1-alpha (HIF-1α) and basic fibroblast growth factor (bFGF) were assessed using western blotting. Finally, the effects of ABZ on tumor growth and radiosensitivity were examined using nude mice xenograft model. Results ABZ significantly improved hypoxia-induced radiation resistance in PC cell line PATU8988 and SW1990 as evidenced by decreased absorbance of MTT, reduced colony number, and increased apoptotic cell ratio. Furthermore, the in vivo results confirmed that ABZ suppressed tumor growth. On mechanisms, treatment with ABZ decreased HIF-1α and bFGF expression levels, which correlated with radioresistance in cells exposed to hypoxia in vitro and tumor to radiation in vivo. Conclusion Taken together, our datas show that HIF-1α and bFGF regulate radiation sensitivity in PC cells under hypoxic conditions. And ABZ enhances radiosensitivity of pancreatic cancer by suppression of HIF-1α and bFGF expression.
MiR-142 modulates human pancreatic cancer proliferation and invasion by targeting hypoxia-inducible factor 1 (HIF-1α) in the tumor microenvironments
