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

被引：15
作者：
Chen, Xue [1 ,2 ]
Yu, Qi [1 ,2 ]
Pan, Hailun [3 ,4 ]
Li, Ping [5 ]
Wang, Xufei [3 ,4 ]
Fu, Shen [1 ,2 ,3 ,6 ]
机构：
[1] Fudan Univ, Dept Radiat Oncol, Shanghai Canc Ctr, 270 Dong An Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China
[3] Fudan Univ, Key Lab Nucl Phys & Ion Beam Applicat MOE, 220 Han Dan Rd, Shanghai 200433, Peoples R China
[4] Fudan Univ, Inst Modern Phys, Shanghai, Peoples R China
[5] Shanghai Proton & Heavy Ion Ctr, Dept Radiat Oncol, Shanghai, Peoples R China
[6] Shanghai Concord Canc Hosp, Dept Radiat Oncol, Shanghai, Peoples R China
来源：
CANCER MANAGEMENT AND RESEARCH | 2020年 / 12卷
基金：
中国国家自然科学基金;
关键词：
IGFBP5; irradiation; prostate cancer; radiosensitivity; PI3K-AKT pathway; FACTOR-BINDING PROTEIN-5; SIGNALING PATHWAY; CELL-CYCLE; GROWTH; RISK; RADIORESISTANCE; METASTASIS; STATISTICS;
D O I：
10.2147/CMAR.S257701
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：5409 / 5418
页数：10
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