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

  • Published online on: April 15, 2016     https://doi.org/10.3892/ijo.2016.3488
  • Pages: 2608-2618
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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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June-2016
Volume 48 Issue 6

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

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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