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Article

Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway

  • Authors:
    • Zhigang Fan
    • Xiaoyi Duan
    • Hui Cai
    • Li Wang
    • Min Li
    • Jingkun Qu
    • Wanjun Li
    • Yongheng Wang
    • Jiansheng Wang
  • View Affiliations / Copyright

    Affiliations: The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
  • Pages: 691-698
    |
    Published online on: June 9, 2015
       https://doi.org/10.3892/or.2015.4044
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Abstract

Invasion and metastasis are the major causes of tumor-related mortality in lung cancer. It is believed that curcumin is an effective drug possessing anti-invasive and anti-metastatic activities in the treatment of cancer. However, the specific mechanisms remain unclear. In the present study, we investigated whether the PKCα/Nox-2/ATF-2/MMP-9 signaling pathway is involved in the invasive behavior of lung cancer and whether curcumin could inhibit invasion by modulating this pathway. The cytotoxic effect of curcumin was evaluated by MTT assay and the capacity of invasion was assessed by Transwell assay. siRNA and plasmid transfection techniques were used to study the function of targeted genes. Real-time PCR and western blot analysis were used to evaluate the expression levels of PKCα, Nox-2, MMP-9 and the phosphorylation of ATF-2. The results showed that curcumin inhibited the proliferation and invasion of A549 cells in a dose-dependent manner. Overexpression of MMP-9 enhanced the invasion of A549 cells. However, inhibition of MMP-9 by siRNA or curcumin suppressed cell invasion. Moreover, we also demonstrated the catalytic role of PKCα in expression of MMP-9 and cellular invasion in A549 cells, which was dependent on the expression of Nox-2 and phosphorylation of ATF-2. Finally, we also showed that curcumin dose-dependently reduced the expression of PKCα, P47phox, Nox-2 and phosphorylated ATF-2, as well as intracellular ROS generation, suggesting the inhibitory effect of curcumin on the activation of the PKCα/Nox-2/ROS/ATF-2 pathway. In conclusion, the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway is activated in lung cancer A549 cells, which could be modulated by curcumin to inhibit cell invasiveness.
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Copy and paste a formatted citation
Spandidos Publications style
Fan Z, Duan X, Cai H, Wang L, Li M, Qu J, Li W, Wang Y and Wang J: Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway. Oncol Rep 34: 691-698, 2015.
APA
Fan, Z., Duan, X., Cai, H., Wang, L., Li, M., Qu, J. ... Wang, J. (2015). Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway. Oncology Reports, 34, 691-698. https://doi.org/10.3892/or.2015.4044
MLA
Fan, Z., Duan, X., Cai, H., Wang, L., Li, M., Qu, J., Li, W., Wang, Y., Wang, J."Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway". Oncology Reports 34.2 (2015): 691-698.
Chicago
Fan, Z., Duan, X., Cai, H., Wang, L., Li, M., Qu, J., Li, W., Wang, Y., Wang, J."Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway". Oncology Reports 34, no. 2 (2015): 691-698. https://doi.org/10.3892/or.2015.4044
Copy and paste a formatted citation
x
Spandidos Publications style
Fan Z, Duan X, Cai H, Wang L, Li M, Qu J, Li W, Wang Y and Wang J: Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway. Oncol Rep 34: 691-698, 2015.
APA
Fan, Z., Duan, X., Cai, H., Wang, L., Li, M., Qu, J. ... Wang, J. (2015). Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway. Oncology Reports, 34, 691-698. https://doi.org/10.3892/or.2015.4044
MLA
Fan, Z., Duan, X., Cai, H., Wang, L., Li, M., Qu, J., Li, W., Wang, Y., Wang, J."Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway". Oncology Reports 34.2 (2015): 691-698.
Chicago
Fan, Z., Duan, X., Cai, H., Wang, L., Li, M., Qu, J., Li, W., Wang, Y., Wang, J."Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway". Oncology Reports 34, no. 2 (2015): 691-698. https://doi.org/10.3892/or.2015.4044
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