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Oxid Med Cell Longev. 2019 Apr 9;2019:1970818. doi: 10.1155/2019/1970818. eCollection 2019.

CIAPIN1 Targeted NHE1 and ERK1/2 to Suppress NSCLC Cells' Metastasis and Predicted Good Prognosis in NSCLC Patients Receiving Pulmonectomy.

Author information

1
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy; Tianjin's Clinical Research Center for Cancer; Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
2
Department of Neuro-Oncology and Neurosurgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
3
Clinical Laboratory, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264000, China.
4
Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang 261053, China.
5
Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
6
Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

Abstract

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.

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