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Article

Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways

  • Authors:
    • Xiangling Xiao
    • Zhongwei He
    • Wei Cao
    • Fen Cai
    • Liang Zhang
    • Qiuyue Huang
    • Chunsheng Fan
    • Chao Duan
    • Xiaobo Wang
    • Jiu Wang
    • Ying Liu
  • View Affiliations / Copyright

    Affiliations: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China, Translational Medical Center, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, Hubei 441300, P.R. China, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
  • Pages: 2608-2618
    |
    Published online on: April 15, 2016
       https://doi.org/10.3892/ijo.2016.3488
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Abstract

Oridonin (Ori), a diterpenoid compound extracted from traditional medicinal herbs, elicits antitumor effects on many cancer types. However, whether Ori can be used in gefitinib-resistant non-small cell lung cancer (NSCLC) cells remains unclear. This study investigated the antitumor activity and underlying mechanisms of Ori. Results demonstrated that this compound dose-dependently inhibited the proliferation, invasion, and migration of the gefitinib-resistant NSCLC cells in vitro. Ori also significantly downregulated the phosphorylation of EGFR, ERK, Akt, expression levels of matrix metalloproteinase-12 (MMP-12), and the cancerous inhibitor of protein phosphatase 2A (CIP2A). In addition, Ori upregulated protein phosphatase 2A (PP2A) activity of gefitinib-resistant NSCLC cells. Ori combined with docetaxel synergistically inhibited these cells. Ori also inhibited tumor growth in murine models. Immunohistochemistry results further revealed that Ori downregulated phospho-EGFR, MMP-12, and CIP2A in vivo. These findings indicated that Ori can inhibit the proliferation, invasion, and migration of gefitinib-resistant NSCLC cells by suppressing EGFR/ERK/MMP-12 and CIP2A/PP2A/Akt signaling pathways. Thus, Ori may be a novel effective candidate to treat gefitinib-resistant NSCLC.
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Copy and paste a formatted citation
Spandidos Publications style
Xiao X, He Z, Cao W, Cai F, Zhang L, Huang Q, Fan C, Duan C, Wang X, Wang J, Wang J, et al: Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways. Int J Oncol 48: 2608-2618, 2016.
APA
Xiao, X., He, Z., Cao, W., Cai, F., Zhang, L., Huang, Q. ... Liu, Y. (2016). Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways. International Journal of Oncology, 48, 2608-2618. https://doi.org/10.3892/ijo.2016.3488
MLA
Xiao, X., He, Z., Cao, W., Cai, F., Zhang, L., Huang, Q., Fan, C., Duan, C., Wang, X., Wang, J., Liu, Y."Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways". International Journal of Oncology 48.6 (2016): 2608-2618.
Chicago
Xiao, X., He, Z., Cao, W., Cai, F., Zhang, L., Huang, Q., Fan, C., Duan, C., Wang, X., Wang, J., Liu, Y."Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways". International Journal of Oncology 48, no. 6 (2016): 2608-2618. https://doi.org/10.3892/ijo.2016.3488
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao X, He Z, Cao W, Cai F, Zhang L, Huang Q, Fan C, Duan C, Wang X, Wang J, Wang J, et al: Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways. Int J Oncol 48: 2608-2618, 2016.
APA
Xiao, X., He, Z., Cao, W., Cai, F., Zhang, L., Huang, Q. ... Liu, Y. (2016). Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways. International Journal of Oncology, 48, 2608-2618. https://doi.org/10.3892/ijo.2016.3488
MLA
Xiao, X., He, Z., Cao, W., Cai, F., Zhang, L., Huang, Q., Fan, C., Duan, C., Wang, X., Wang, J., Liu, Y."Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways". International Journal of Oncology 48.6 (2016): 2608-2618.
Chicago
Xiao, X., He, Z., Cao, W., Cai, F., Zhang, L., Huang, Q., Fan, C., Duan, C., Wang, X., Wang, J., Liu, Y."Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways". International Journal of Oncology 48, no. 6 (2016): 2608-2618. https://doi.org/10.3892/ijo.2016.3488
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