CIAPIN1 Targeted NHE1 and ERK1/2 to Suppress NSCLC Cells' Metastasis and Predicted Good Prognosis in NSCLC Patients Receiving Pulmonectomy
CIAPIN1 Targeted NHE1 and ERK1/2 to Suppress NSCLC Cells' Metastasis and Predicted Good Prognosis in NSCLC Patients Receiving Pulmonectomy
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CIAPIN1 靶向 NHE1 和 ERK1/2 抑制 NSCLC 细胞转移并预测接受肺切除术的 NSCLC 患者的良好预后
DOI：
10.1155/2019/1970818
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Yang, Lili
中科院分区：
文献类型：
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作者：
Wang, Jian;Zhou, Ying;Yang, Lili
目的细胞因子诱导的凋亡抑制因子1（CIAPIN 1）作为受体酪氨酸激酶-Ras信号通路的下游效应子，已被报道为多种肿瘤的候选抑癌基因。本研究旨在探讨CIAPIN 1对非小细胞肺癌（NSCLC）患者预后的影响以及CIAPIN 1对NSCLC A549细胞转移的影响。方法采用Western blot方法检测CIAPIN 1在NSCLC中的表达，Kaplan-Meier生存分析分析CIAPIN 1对NSCLC患者预后的影响。采用创伤愈合实验、Transwell小室侵袭实验和裸鼠成瘤实验检测A549细胞的转移潜能。结果在随访期间，我们发现CIAPIN 1过表达表明良好的生存期。CIAPIN 1过表达抑制A549细胞的迁移、侵袭、MMPs和EMT相关标志物。此外，NHE 1（Na+/H+交换器1）表达和ERK 1/2磷酸化沿着CIAPIN 1上调而降低。重要的是，用NHE 1特异性抑制剂Cariporide处理CIAPIN 1过表达的A549细胞，进一步抑制了转移能力、MMP表达、EMT相关标志物和磷酸化ERK 1/2。用MEK 1特异性抑制剂PD 98059治疗诱导了与Cariporide观察到的几乎相同的CIAPIN 1过表达依赖性转移能力、MMP表达和EMT相关标志物的抑制。此外，Cariporide和PD 98059发挥协同抑制A549细胞的转移能力。结论CIAPIN 1的高表达可能对NSCLC的抑制有重要作用，提示CIAPIN 1的高表达可能与化疗药物联合应用治疗NSCLC。
Objective Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) acts as a downstream effector of the receptor tyrosine kinase-Ras signaling pathway and has been reported as a candidate tumor suppressor gene in various cancers. Our current study was aimed at investigating the prognostic impact of CIAPIN1 on Non-Small-Cell Lung Carcinoma (NSCLC) patients and the effect of CIAPIN1 on NSCLC A549 cells' metastasis. Methods Western blot analysis was applied to detect CIAPIN1 expression; Kaplan-Meier survival analysis was used to evaluate the effect of CIAPIN1 on NSCLC patients' prognosis. Wound healing assay, Transwell chamber invasion analysis, and tumorigenicity assay in BALB/c nude mice were used to measure the metastasis potential of A549 cells. Results We found that CIAPIN1 overexpression indicated good survival duration during the follow-up period. CIAPIN1 overexpression inhibited the migration, invasion, MMPs, and EMT-associated markers in A549 cells. Further, NHE1 (Na+/H+ exchanger 1) expression and ERK1/2 phosphorylation decreased along with CIAPIN1 upregulation. Importantly, treating A549 cells with CIAPIN1 overexpression with the NHE1-specific inhibitor, Cariporide, further inhibited the metastatic capacity, MMP expression, EMT-associated markers, and phosphorylated ERK1/2. Treatment with the MEK1-specific inhibitor, PD98059, induced nearly the same suppression of CIAPIN1 overexpression-dependent metastatic capacity, MMP expression, and EMT-associated markers as was observed with Cariporide. Further, Cariporide and PD98059 exert synergistical suppression of A549 cells' metastatic capacity. Conclusion Thus, the current results implied a potential management by which CIAPIN1 upregulation may have a crucial effect on the suppression of NSCLC, indicating that overexpression of CIAPIN1 might serve as a combination with chemotherapeutical agents in NSCLC therapy.