The Ibr-7 Derivative of Ibrutinib Exhibits Radiosensitivity in Pancreatic Cancer Cells via Targeting EGFR

Abstract

Background: Radiotherapy is one of the main therapeutic methods for pancreatic cancer, but radiation resistance limits the clinical application. As a result, novel therapeutic agents to improve the radiosensitivity is urgent. This study aimed to investigate the effect of Ibr-7 (the derivative of ibrutinib) on radiosensitivity of human pancreatic cancer cells.Methods: The effect of Ibr-7 on pancreatic cancer cell’s proliferation were detected by CCK-8 assay. Radiosensitivity was assessed by clonogenic formation assay. Cell cycle, cell apoptosis were analyzed by flow cytometry. DNA damage was detected by immunofluorescence analysis. The expression of p-EGFR, EGFR were determined by western blot.Results: Ibr-7 showed anti-proliferative effect in PANC-1 and Capan2 cells in a dose- and time-dependent manner. Ibr-7 (2 µmol/L) enhanced the effect of radiation in PANC-1 and Capan2 cells. Further findings showed that this combination enhanced G2/M phase arrest and increased cell apoptosis. Additional molecular mechanism studies revealed that the expression of p-EGFR was decreased by Ibr-7 alone or combined with radiation. Overexpression of EGFR reversed the cell apoptosis induced by Ibr-7 combined with radiation. Moreover, the expression of γ-H2AX was significantly decreased in Ibr-7 combined with radiation group.Conclusions: Our study indicated that the potential application of Ibr-7 as a highly effective radiosensitizer for the treatment of pancreatic cancer cells.