Ephrin type‑A receptor 2 regulates sensitivity to paclitaxel in nasopharyngeal carcinoma via the phosphoinositide 3‑kinase/Akt signalling pathway.

Ephrin type‑A receptor 2 regulates sensitivity to paclitaxel in nasopharyngeal carcinoma via the phosphoinositide 3‑kinase/Akt signalling pathway.
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Ephrin A 型受体 2 通过磷酸肌醇 3 激酶/Akt 信号通路调节鼻咽癌对紫杉醇的敏感性。

DOI:
10.3892/mmr.2014.2799
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发表时间:
2015-02
影响因子:
3.4
通讯作者:
Tian Y
Tian Y
中科院分区:
医学4区
文献类型:
--
作者:
Wang Y;Liu Y;Li G;Su Z;Ren S;Tan P;Zhang X;Qiu Y;Tian Y

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肝配蛋白A型受体2(EphA 2)是与癌细胞转移相关的受体酪氨酸激酶。关于其对鼻咽癌(NPC)紫杉醇敏感性调节的影响,研究很少。在本研究中,与暴露于相同浓度的紫杉醇的对照细胞相比,EphA 2表达的上调增强了NPC 5- 8 F细胞的存活。流式细胞术和western blot分析表明,EphA 2过表达降低鼻咽癌细胞对紫杉醇的敏感性,通过调节紫杉醇介导的细胞周期进程,而不是在体外凋亡。这是伴随着细胞周期蛋白依赖性激酶抑制剂,p21和p27,和非活性磷酸化视网膜母细胞瘤蛋白的表达的改变。此外,紫杉醇刺激和EphA 2过表达导致NPC细胞中磷酸肌醇3-激酶(PI 3 K)/Akt信号通路的激活。PI 3 K/Akt信号传导途径的抑制恢复了过表达EphA 2的5- 8 F细胞对紫杉醇的敏感性,这表明PI 3 K/Akt途径参与EphA 2介导的紫杉醇敏感性。目前的研究表明,EphA 2介导的敏感性紫杉醇通过调节PI 3 K/Akt信号通路在NPC。
Ephrin type-A receptor 2 (EphA2) is a receptor tyrosine kinase that is associated with cancer cell metastasis. There has been little investigation into its impact on the regulation of sensitivity to paclitaxel in nasopharyngeal carcinoma (NPC). In the present study, upregulation of EphA2 expression enhanced the survival of NPC 5-8F cells, compared with control cells exposed to the same concentrations of paclitaxel. Flow cytometry and western blot analysis demonstrated that over-expression of EphA2 decreased NPC cancer cell sensitivity to paclitaxel by regulating paclitaxel-mediated cell cycle progression but not apoptosis in vitro. This was accompanied by alterations in the expression of cyclin-dependent kinase inhibitors, p21 and p27, and of inactive phosphorylated-retinoblastoma protein. Furthermore, paclitaxel stimulation and EphA2 over-expression resulted in activation of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway in NPC cells. Inhibition of the PI3K/Akt signalling pathway restored sensitivity to paclitaxel in 5-8F cells over-expressing EphA2, which indicated that the PI3K/Akt pathway is involved in EphA2-mediated paclitaxel sensitivity. The current study demonstrated that EphA2 mediates sensitivity to paclitaxel via the regulation of the PI3K/Akt signalling pathway in NPC.
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