Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer.
Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer.
复制标题
胰岛素样生长因子结合蛋白 3 通过抑制前列腺癌中的 mTOR 通路介导白细胞介素 24 诱导的细胞凋亡
DOI：
10.3892/or.2015.4201
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发表时间：
2015-11
期刊：
影响因子：
4.2
通讯作者：
He D
中科院分区：
文献类型：
--
作者：
Du Y;Long Q;Shi Y;Liu X;Li X;Zeng J;Gong Y;Li L;Wang X;He D
胰岛素样生长因子结合蛋白-3（IGFBP-3）以非胰岛素样生长因子（IGF）依赖的方式在多种细胞系统中诱导细胞凋亡，但其分子机制尚不清楚。在本研究中，我们发现IGFBP-3显着增强白细胞介素-24（IL-24）诱导的前列腺癌（PC）细胞系在体外的细胞死亡。向细胞培养基中添加IGFBP-3或在PC细胞系中强制表达IGFBP-3都抑制了哺乳动物雷帕霉素靶蛋白（mTOR）的活化。mTOR/S6 K的下调降低了Mcl-1蛋白的表达，从而促进了对IL-24处理的敏感性。过表达Mcl-1可降低IL-24和IGFBP-3诱导的PARP水平，提示IL-24诱导的细胞凋亡是通过Mcl-1实现的。然后，我们表明IL-24和IGFBP-3的组合在体内显著抑制PC肿瘤生长。我们建议IGFBP-3和IL-24无毒mTOR抑制剂可用作PC治疗中的佐剂。
IGF-binding protein-3 (IGFBP-3) has been shown to induce apoptosis in an insulin-like growth factor (IGF)-independent manner in various cell systems, however, the underlying molecular mechanisms remain unknown. In the present study, we showed that IGFBP-3 significantly enhanced interleukin-24 (IL-24)-induced cell death in prostate cancer (PC) cell lines in vitro. Both the addition of IGFBP-3 to cell medium or the enforced expression of IGFBP-3 in the PC cell line inhibited activation of mammalian target of rapamycin (mTOR). Downregulation of mTOR/S6K reduced Mcl-1 protein expression and consequently promoted sensitization to IL-24 treatment. Overexpression of Mcl-1 reduced the level of cleaved poly(ADP-ribose) polymerase (PARP) induced by IL-24 and IGFBP-3, suggesting that the IL-24-induced apop-tosis is realized by way of Mcl-1. We then showed that the combination of IL-24 and IGFBP-3 significantly suppressed PC tumor growth in vivo. We propose that the IGFBP-3 and IL-24 non-toxic mTOR inhibitors can be used as an adjuvant in the treatment of PC.
影响因子：
7.4
作者：
Fabbri, Francesco;Brigliadori, Giovanni;Carloni, Silvia;Ulivi, Paola;Vannini, Ivan;Tesei, Anna;Silvestrini, Rosella;Amadori, Dino;Zoli, Wainer
通讯作者：
Zoli, Wainer