The Ibr-7 derivative of ibrutinib radiosensitizes pancreatic cancer cells by downregulating p-EGFR
| Autor: | Rong Dong, Youyou Yan, Bo Zhang, Qingyu Li, Fei Wang, Nengming Lin, Biqin Tan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Radiosensitizer EGFR medicine.medical_treatment Apoptosis lcsh:RC254-282 Flow cytometry Radiosensitivity 03 medical and health sciences 0302 clinical medicine Pancreatic cancer Genetics medicine lcsh:QH573-671 Clonogenic assay 030304 developmental biology 0303 health sciences medicine.diagnostic_test lcsh:Cytology Chemistry Cell cycle lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Radiation therapy Oncology 030220 oncology & carcinogenesis Cancer research Ibr-7 Primary Research |
| Zdroj: | Cancer Cell International Cancer Cell International, Vol 20, Iss 1, Pp 1-11 (2020) |
| ISSN: | 1475-2867 |
| DOI: | 10.1186/s12935-020-01548-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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