Klotho suppresses growth and invasion of colon cancer cells through inhibition of IGF1R-mediated PI3K/AKT pathway
Klotho suppresses growth and invasion of colon cancer cells through inhibition of IGF1R-mediated PI3K/AKT pathway
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DOI：
10.3892/ijo.2014.2430
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发表时间：
2014-08-01
影响因子：
5.2
通讯作者：
Cai, San-Jun
中科院分区：
文献类型：
--
作者：
Li, Xin-Xiang;Huang, Li-Yong;Cai, San-Jun
Klotho （KL）最初被认为是一种衰老抑制基因，并已被确定为包括结肠癌在内的多种癌症的肿瘤抑制基因。然而，KL在结肠癌中的潜在作用和分子事件尚不清楚。本研究旨在通过免疫组织化学方法研究KL在人结肠癌中的表达情况，分析KL表达与结肠癌患者临床病理特征的相关性。利用慢病毒介导的KL表达获得后的功能分析来评估肿瘤在体外和体内对结肠癌细胞的生长和侵袭。与癌旁非癌组织（ANCT）相比，癌组织中KL表达率显著降低（60.3 vs.77.9%， P=0.022）， KL表达与Dukes分期（P=0.034）和肿瘤浸润深度（P=0.008）呈负相关。体外过表达KL抑制了结肠癌细胞的增殖活性和侵袭潜能，并降低了p-IGF1R、p-PI3K、p-AKT、PCNA和MMP-2的表达。慢病毒介导的KL载体（Lv-KL）处理HT-29皮下肿瘤模型后，其肿瘤体积明显小于阴性对照（NC）组(P
Klotho (KL) was originally characterized as an aging suppressor gene, and has been identified as a tumor suppressor gene in a variety of cancers including colon cancer. However, the potential role and molecular events for KL in colon cancer remain unclear. The present study aimed to investigate the expression of KL in human colon cancer by immunohistochemistry, and to analyze the correlation between KL expression and clinicopathological characteristics of patients with colon cancer. Functional analysis after lentivirus-mediated gain of KL expression was used to assess the tumor growth and invasion in colon cancer cells in vitro and in vivo. The rate of KL expression was significantly decreased in cancer tissues compared with that in adjacent non-cancer tissues (ANCT) (60.3 vs.77.9%, P=0.022), and KL expression was negatively associated with Dukes staging (P=0.034) and depth of tumor invasion (P=0.008). Overexpression of KL in vitro inhibited cell proliferative activities and invasive potential in colon cancer cells, companied with decreased expression of p-IGF1R, p-PI3K, p-AKT, PCNA and MMP-2. In addition, the tumor volumes in the HT-29 subcutaneous tumor model treated with lentivirus-mediated KL vector (Lv-KL) was significantly smaller than those of the negative control (NC) group (P