Hyperthermia Enhances the Radiosensitivity of Pancreatic Cancer Cells by Inhibiting Wnt2B Signaling

Abstract

Pancreatic cancer (PC) is a highly lethal human malignance. Due to unobvious symptoms at early stage, most of the patients with PC are diagnosed at late stages and lose the chance of surgical resection. Furthermore, PC patients are resistant to chemoradiotherapy and therefore show a dismal survival. Hyperthermia is commonly used as a sensitizer of chemotherapy or radiotherapy for the clinical treatment of human cancers. Our study aimed to investigate whether hyperthermia can improve the radiosensitivity of PC cells and uncover the involved mechanisms. PC cells BxPC3, CFPAC-1 and PANC1 were heated to 43 ℃ 1 h before exposure to ionizing irradiation (IR). The radiosensitivity of PC cells were detected in vitro by colony formation assay, immunofluence analysis and western blotting. The mechanisms studies have been conducted using qRT-PCR analysis, cDNA/siRNA transfection and comet assay. Hyperthermia significantly enhanced the radiosensitivity of PC cells by decreasing their colony formation and increasing DNA damage following IR. By qRT-PCR analysis of Wnt genes expressions, we found Wnt2B was significantly down-regulated in PC-3 cells which were treated with the combination of hyperthermia and IR compared with hyperthermia or IR alone. Functional assays showed that the expression level of Wnt2B was inversely associated with the radiosensitivity of PC-3 cells. Furthermore, we found hyperthermia inhibited the expression of DNA repair proteins such as p-BRCA1 and p-MRE11 in PC cells following IR CONCLUSION: Hyperthermia can significantly enhance the radiosensitivity of PC cells in a Wnt2B signaling-dependent manner.