Netrin‑1 interference potentiates epithelial‑to‑mesenchymal transition through the PI3K/AKT pathway under the hypoxic microenvironment conditions of non‑small cell lung cancer

  • Authors:
    • Xiayun Jin
    • Heqi Luan
    • Hua Chai
    • Lina Yan
    • Jing Zhang
    • Qi Wang
    • Lihua Cao
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  • Published online on: February 15, 2019     https://doi.org/10.3892/ijo.2019.4716
  • Pages: 1457-1465
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Abstract

Netrin‑1 is overexpressed in several types of cancer. However, whether netrin‑1 can potentiate hypoxia‑induced tumor progression in lung cancer has not been reported to date. Thus, the objective of the present study was to investigate whether netrin‑1 regulates cancer cell migration and invasion under hypoxic conditions in lung cancer and explore the underlying mechanism. A three‑dimensional microfluidic chip was used to observe real‑time changes in cancer cells, and cobalt chloride (CoCl2) was used to simulate a hypoxic microenvironment. Netrin‑1 siRNA was employed in the A549 and PC9 cell lines to downregulate the expression of netrin‑1. Microfluidic chip, wound healing and Transwell assays were used to examine cell migration and invasion. The expression levels of E‑cadherin and vimentin were detected by western blotting. The data demonstrated that netrin‑1 mediated epithelial‑to‑mesenchymal transition (EMT) of A549 and PC9 cells in vitro, which may be associated with the phosphoinositide 3 kinase/AKT pathway. This effect of netrin‑1 on the EMT was not observed in the normoxic microenvironment. In this retrospective study, netrin‑1 concentrations were evaluated in serum obtained from patients with non‑small cell lung cancer (NSCLC) and compared with healthy control samples by quantitative enzyme‑linked immunosorbent analysis. The serum concentration of netrin‑1 was found to be significantly higher in NSCLC patients compared with that in healthy donors. Taken together, the findings of the present study highlight a novel role for netrin‑1 in tumor development under hypoxia in NSCLC and provide further evidence for the use of netrin‑1 as a therapeutic target.
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April-2019
Volume 54 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Jin X, Luan H, Chai H, Yan L, Zhang J, Wang Q and Cao L: Netrin‑1 interference potentiates epithelial‑to‑mesenchymal transition through the PI3K/AKT pathway under the hypoxic microenvironment conditions of non‑small cell lung cancer. Int J Oncol 54: 1457-1465, 2019
APA
Jin, X., Luan, H., Chai, H., Yan, L., Zhang, J., Wang, Q., & Cao, L. (2019). Netrin‑1 interference potentiates epithelial‑to‑mesenchymal transition through the PI3K/AKT pathway under the hypoxic microenvironment conditions of non‑small cell lung cancer. International Journal of Oncology, 54, 1457-1465. https://doi.org/10.3892/ijo.2019.4716
MLA
Jin, X., Luan, H., Chai, H., Yan, L., Zhang, J., Wang, Q., Cao, L."Netrin‑1 interference potentiates epithelial‑to‑mesenchymal transition through the PI3K/AKT pathway under the hypoxic microenvironment conditions of non‑small cell lung cancer". International Journal of Oncology 54.4 (2019): 1457-1465.
Chicago
Jin, X., Luan, H., Chai, H., Yan, L., Zhang, J., Wang, Q., Cao, L."Netrin‑1 interference potentiates epithelial‑to‑mesenchymal transition through the PI3K/AKT pathway under the hypoxic microenvironment conditions of non‑small cell lung cancer". International Journal of Oncology 54, no. 4 (2019): 1457-1465. https://doi.org/10.3892/ijo.2019.4716