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Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Ibrutinib | Primary research

The Ibr-7 derivative of ibrutinib radiosensitizes pancreatic cancer cells by downregulating p-EGFR

Authors: Biqin Tan, Rong Dong, Bo Zhang, Youyou Yan, Qingyu Li, Fei Wang, Nengming Lin

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Radiotherapy is one of the main treatments for pancreatic cancer, but radiation resistance limits its clinical application. As a result, novel therapeutic agents to improve radiosensitivity are urgently needed. This study aimed to investigate the effect of Ibr-7 (a derivative of ibrutinib) on the radiosensitivity of human pancreatic cancer cells.

Methods

The effect of Ibr-7 on pancreatic cancer cell proliferation was detected by CCK-8 assays. Radiosensitivity was assessed by clonogenic formation assays. Cell cycle and cell apoptosis were analysed by flow cytometry. DNA damage was evaluated by immunofluorescence analysis. The expression levels of PARP, Cleaved caspase 3, p-EGFR and EGFR were determined by western blot.

Results

Ibr-7 showed an anti-proliferative effect on PANC-1 and Capan2 cells in a dose- and time-dependent manner. Ibr-7 (2 μmol/L) enhanced the effect of radiation on 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 in combination with radiation. Overexpression of p-EGFR reversed the cell apoptosis induced by Ibr-7 combined with radiation. Moreover, the expression of γ-H2AX was significantly decreased in the Ibr-7 plus radiation group.

Conclusions

Our study indicated the potential application of Ibr-7 as a highly effective radiosensitizer for the treatment of pancreatic cancer cells.
Appendix
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Metadata
Title
The Ibr-7 derivative of ibrutinib radiosensitizes pancreatic cancer cells by downregulating p-EGFR
Authors
Biqin Tan
Rong Dong
Bo Zhang
Youyou Yan
Qingyu Li
Fei Wang
Nengming Lin
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01548-6

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