Silencing Kif2a induces apoptosis in squamous cell carcinoma of the oral tongue through inhibition of the PI3K/Akt signaling pathway

Silencing Kif2a induces apoptosis in squamous cell carcinoma of the oral tongue through inhibition of the PI3K/Akt signaling pathway
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沉默 Kif2a 通过抑制 PI3K/Akt 信号通路诱导口腔舌鳞状细胞癌凋亡

DOI:
10.3892/mmr.2013.1804
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发表时间:
2014-01-01
影响因子:
3.4
通讯作者:
Wei, Fengcai
Wei, Fengcai
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Ketao;Lin, Changlong;Wei, Fengcai

文献摘要

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已有研究表明,Kif2a的过表达参与了口腔舌鳞癌(SCCOT)的进展、侵袭和转移。很少有研究报道Kif2a与肿瘤细胞凋亡的相关性,Kif2a参与哪些信号通路尚不清楚。磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B (Akt)通路在许多类型的人类癌症中经常被激活。本研究的目的是研究Kif2表达下调对Tca8113细胞P13K/Akt通路的影响,以确定沉默Kif2是否会抑制P13K/Akt通路,导致细胞凋亡。构建siRNA载体,western blot检测RNA干扰程度,流式细胞术检测Tca8113细胞凋亡促进程度。结果显示,沉默Kif2a可诱导Tca8113细胞凋亡,降低PI3K、Akt和b细胞淋巴瘤2 (Bcl-2) mRNA和蛋白水平。pi3k特异性激动剂胰岛素样生长因子1 (IGF-1)通过磷酸化Akt消除Tca8113-Kif2a细胞凋亡上调。结果表明,沉默Kif2a至少部分通过PI3K/Akt信号通路诱导肿瘤细胞凋亡。
Previous studies have demonstrated that the overexpression of Kif2a is involved in the progression, invasion and metastasis of squamous cell carcinoma of the oral tongue (SCCOT). Few studies have reported the correlation between Kif2a and apoptosis of tumor cells and which signaling pathways Kif2a is involved in remains unclear. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway is frequently activated in many types of human cancer. The aim of the present study was to investigate the effects of downregulation of Kif2 expression on the P13K/Akt pathway in Tca8113 cells to determine whether silencing of Kif2 inhibits the P13K/Akt pathway, resulting in cell apoptosis. siRNA vector was constructed, western blot analysis was used to determine RNA interference and flow cytometry was used to determine promotion of Tca8113 cell apoptosis. The results revealed that silencing Kif2a induces apoptosis and decreases the mRNA and protein level of PI3K, Akt and B-cell lymphoma 2 (Bcl-2) in Tca8113 cells. The PI3K-specific agonist insulin-like growth factor 1 (IGF-1) eliminated the upregulation of apoptosis of Tca8113-Kif2a cells by phosphorylation of Akt. The results suggest that silencing Kif2a induces tumor cell apoptosis, at least partially, through the PI3K/Akt signaling pathway.