Inhibition of lung cancer cells growth, motility and induction of apoptosis by Klotho, a novel secreted Wnt antagonist, in a dose-dependent manner
Inhibition of lung cancer cells growth, motility and induction of apoptosis by Klotho, a novel secreted Wnt antagonist, in a dose-dependent manner
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Klotho（一种新型分泌型 Wnt 拮抗剂）以剂量依赖性方式抑制肺癌细胞生长、运动并诱导细胞凋亡
DOI：
10.4161/cbt.21420
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发表时间：
2012-10-01
影响因子：
3.6
通讯作者：
Wu, Jianqing
中科院分区：
文献类型：
--
作者：
Chen, Bo;Ma, Xiaoli;Wu, Jianqing
Klotho （KL）是一种可以脱落的跨膜蛋白，作为循环激素并调节多种信号通路。Klotho mRNA也存在一个剪接变体，它编码一种推定的分泌蛋白（Klotho- s, KL-S），在人和小鼠中都存在。最近发现潜在的抗衰老基因Klotho参与了几种不同人类癌症的进展。在本次研究中，我们进行了Klotho在肺癌细胞系A549中的表达和活性的研究。采用RT-PCR和western blotting检测Klotho的表达。采用MTT和划痕运动法观察Klotho对细胞生长和运动的影响，TUNEL法观察Klotho对细胞凋亡的影响。western blotting检测Wnt信号通路活性。我们发现Klotho在A549细胞中内源性表达，但与正常肺组织相比表达水平较低。过表达KL或KL- s可抑制细胞的增殖、运动并诱导细胞凋亡，且呈剂量依赖性。此外，我们报道KL可以抑制Wnt -TCF/ β -catenin信号通路的激活，并参与KL诱导的生长抑制。这些研究表明Klotho在肺癌中具有潜在的抑瘤作用，并提示Klotho的抑瘤活性可能是通过其KL-S异构体介导的。这些结果表明，使用Klotho或KL-S作为开发新型肺癌治疗干预措施的潜在策略。
Klotho (KL) is a transmembrane protein that can be shed, and act as a circulating hormone and modulate several signaling pathways. There also exists a splice variant of Klotho mRNA, which encodes a putative secreted protein (Klotho-S, KL-S) in both human and mouse. The potential anti-senescence gene Klotho has been recently found to participate in the progression of several different human cancers. In the current study, we undertook to study the expression and activity of Klotho in lung cancer cell line A549. Klotho expression was studied by using RT-PCR and western blotting. Effects of Klotho on cell growth and motility were assessed using MTT and scratch motility assay, and the apoptosis was assessed by TUNEL. Wnt signaling pathway activity was measured by western blotting. We established that the Klotho was endogenous expressed in A549 cells, but the expression level is lower compared with normal lung tissues. The overexpression of KL or KL-S could inhibit the cell proliferation, motility, and induce apoptosis in a dose-dependent manner. Also, we report KL could inhibit activation of Wnt -TCF/beta-catenin signaling pathway, and it is involved in KL-induced growth inhibition. These studies indicate Klotho works as a potential tumor suppressor in lung cancer, and suggest that the Klotho tumor suppressive activities could be mediated through its KL-S isoform. These results suggest the use of Klotho or KL-S as potential strategy for the development of novel therapeutic interventions for lung cancers.