Overexpression of IGFBP5 Enhances Radiosensitivity Through PI3K-AKT Pathway in Prostate Cancer

Xue Chen; Qi Yu; Hailun Pan; Ping Li; Xufei Wang; Shen Fu

doi:10.2147/CMAR.S257701

Overexpression of IGFBP5 Enhances Radiosensitivity Through PI3K-AKT Pathway in Prostate Cancer

Cancer Manag Res. 2020 Jul 6:12:5409-5418. doi: 10.2147/CMAR.S257701. eCollection 2020.

Authors

Xue Chen^{1

2}, Qi Yu^{1

2}, Hailun Pan^{3

4}, Ping Li⁵, Xufei Wang^{3

4}, Shen Fu^{1

2

3

6}

Affiliations

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
³ Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China.
⁴ Institute of Modern Physics, Fudan University, Shanghai, People's Republic of China.
⁵ Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People's Republic of China.
⁶ Department of Radiation Oncology, Shanghai Concord Cancer Hospital, Shanghai, People's Republic of China.

Abstract

Background: 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; PI3K-AKT pathway; irradiation; prostate cancer; radiosensitivity.

Grants and funding

This study was supported by the National Key Research and Development Program of China (No. 2017YFC0107600), the National Natural Science Foundation of China (Nos. 81773225; 11375047; 11005019).