Cancer Management and Research (Jul 2020)
Overexpression of IGFBP5 Enhances Radiosensitivity Through PI3K-AKT Pathway in Prostate Cancer
Abstract
Xue Chen,1,2 Qi Yu,1,2 Hailun Pan,3,4 Ping Li,5 Xufei Wang,3,4 Shen Fu1– 3,6 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People’s Republic of China; 4Institute of Modern Physics, Fudan University, Shanghai, People’s Republic of China; 5Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China; 6Department of Radiation Oncology, Shanghai Concord Cancer Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Shen FuDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai 200032, People’s Republic of ChinaTel/Fax +86-021-64175590Email [email protected] WangKey Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, 220 Han Dan Road, Shanghai 200433, People’s Republic of ChinaTel +86-021-55665471Fax +86-021-65642787Email [email protected]: Radiotherapy is the main treatment for localized prostate cancer. The therapeutic effects of radiotherapy are highly dependent on radiosensitivity of target tumors. Here, we investigated the impact of insulin-like growth factor-binding protein 5 (IGFBP5) on irradiation therapy in prostate cancer.Methods: IGFBP5 gene was overexpressed in human prostate cancer cell lines, PC3 and DU145, with transfection of lentivirus expression vector. Radiosensitivity of the cell lines was assessed with colony formation, cell cycle and cell proliferation assays. The expression of proteins associated with the PI3K-AKT pathway was determined by Western blotting. The effect of IGFBP5 knockdown on PI3K-AKT pathway was tested using PI3K inhibitor.Results: Higher expression of IGFBP5 improved the efficacy of radiotherapy for prostate cancer patients. The effects of IGFBP5 were linked to the PI3K-AKT signaling pathway. Overexpression of IGFBP5 enhanced radiosensitivity and induced G2/M phase arrest in prostate cancer cells. In contrast, it decreased PI3K, p-AKT expression and cell viability. These effects were reversed by IGFBP5 knockdown.Conclusion: Our results reveal that IGFBP5 regulates radiosensitivity in prostate cancer via the PI3K-AKT pathway. It is, therefore, a potential biomarker of tumors that influences the therapeutic effect of radiotherapy.Keywords: IGFBP5, irradiation, prostate cancer, radiosensitivity, PI3K-AKT pathway
