Overexpression of IGFBP5 Enhances Radiosensitivity Through PI3K-AKT Pathway in Prostate Cancer
Overexpression of IGFBP5 Enhances Radiosensitivity Through PI3K-AKT Pathway in Prostate Cancer
复制标题
IGFBP5 的过度表达通过 PI3K-AKT 途径增强前列腺癌的放射敏感性
DOI：
10.2147/cmar.s257701
复制
发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Fu, Shen
中科院分区：
文献类型：
--
作者：
Chen, Xue;Yu, Qi;Fu, Shen
背景：放射治疗是局限性前列腺癌的主要治疗手段。放射治疗的疗效高度依赖于靶肿瘤的放射敏感性。本研究旨在探讨胰岛素样生长因子结合蛋白5（IGFBP 5）在前列腺癌放射治疗中的作用。方法：采用慢病毒表达载体转染人前列腺癌细胞系PC 3和DU 145，使IGFBP 5基因在细胞内过表达。用集落形成、细胞周期和细胞增殖试验评估细胞系的放射敏感性。通过蛋白质印迹法测定与PI 3 K-AKT通路相关的蛋白质的表达。结果：IGFBP 5的高表达可提高前列腺癌患者的放疗疗效。IGFBP 5的作用与PI 3 K-AKT信号通路有关。IGFBP 5过表达增强前列腺癌细胞的放射敏感性并诱导G2/M期阻滞。相反，它降低PI 3 K，p-AKT表达和细胞活力。结论：IGFBP 5通过PI 3 K-AKT通路调节前列腺癌的放射敏感性。因此，它是一种潜在的肿瘤生物标志物，影响放射治疗的疗效。
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.