Department of Radiation Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, P.R. China.
Mol Med Rep. 2012 Dec;6(6):1433-7. doi: 10.3892/mmr.2012.1110. Epub 2012 Sep 28.
Secretory clusterin (sCLU) is a type of stress-induced, pro-survival glycoprotein elevated in early-stage cancer. It enhances cancer cell survival and is associated with several types of cancer progression. In this study, we measured the PI3K/AKT signaling activity by determining the phosphorylation level of the AKT protein, namely pAKT. A549 human non-small cell lung carcinoma (NSCLC) cells were treated with insulin-like growth factor-1 (IGF-1) for various periods of time. The results showed that IGF-1 activated the PI3K/AKT signaling pathway in the A549 cells in a time-dependent manner. Western blot analysis was performed to determine the expression of sCLU protein in A549 cells treated with IGF-1. IGF-1 elevated the expression of sCLU. To determine whether sCLU is required for the IGF-1 activation of the PI3K/AKT signaling pathway, the A549 cells were treated with IGF-1 and sCLU antisense oligonuleotide (sCLU ASO). sCLU ASO blocked the IGF-1 activation of the PI3K/AKT signaling pathway. These results demonstrate that IGF-1 activates the P13K/AKT signaling pathway via the upregulation of sCLU. The present study implies that this pathway may uncover a new mechanism for cancer progression and reveal new targets for drug development in the treatment of NSCLC.
分泌型簇蛋白（sCLU）是一种应激诱导的、促生存糖蛋白，在早期癌症中升高。它增强了癌细胞的存活能力，并与几种类型的癌症进展有关。在这项研究中，我们通过测定 AKT 蛋白的磷酸化水平，即 pAKT，来测量 PI3K/AKT 信号转导活性。用胰岛素样生长因子-1（IGF-1）处理 A549 人非小细胞肺癌（NSCLC）细胞不同时间。结果表明，IGF-1 以时间依赖的方式激活 A549 细胞中的 PI3K/AKT 信号通路。用 Western blot 分析测定 IGF-1 处理的 A549 细胞中 sCLU 蛋白的表达。IGF-1 升高了 sCLU 的表达。为了确定 sCLU 是否是 IGF-1 激活 PI3K/AKT 信号通路所必需的，用 IGF-1 和 sCLU 反义寡核苷酸（sCLU ASO）处理 A549 细胞。sCLU ASO 阻断了 IGF-1 对 PI3K/AKT 信号通路的激活。这些结果表明，IGF-1 通过上调 sCLU 激活 P13K/AKT 信号通路。本研究表明，该通路可能揭示了癌症进展的新机制，并为治疗 NSCLC 的药物开发揭示了新的靶点。
