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Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines

  • Authors:
    • Ke Li
    • Fangzheng Zhou
    • Yu Zhou
    • Sheng Zhang
    • Qianwen Li
    • Zhenyu Li
    • Li Liu
    • Gang Wu
    • Rui Meng
  • View Affiliations / Copyright

    Affiliations: Pharmacy Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 437-446
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    Published online on: May 30, 2019
       https://doi.org/10.3892/ijmm.2019.4220
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Abstract

The abnormal activation of the downstream signaling pathways of epidermal growth factor receptor (EGFR) that are independent of EGFR, contribute to the acquisition of EGFR‑tyrosine kinase inhibitor (TKI) resistance in non‑small cell lung cancer (NSCLC). The serine/threonine protein kinase casein kinase II (CK2) phosphorylates and modulates several members of the EGFR downstream signaling pathways. Thus, the purpose of the current study was to investigate the effects of the addition of quinalizarin (a specific CK2 inhibitor) to icotinib (an EGFR‑TKI) on the proliferation and apoptosis of four NSCLC cell lines and its underlying mechanisms. The human lung adenocarcinoma cell lines HCC827, A549, H1650 and H1975 were employed to represent the EGFR‑TKI‑sensitive EGFR (EGFR‑sensitive) mutation, wild‑type EGFR and the EGFR‑TKI‑resistant EGFR (EGFR‑resistant) mutations. The cell viability was determined by the MTT assay. Cell apoptosis was detected by flow cytometry using the Annexin V‑enhanced green fluorescent protein Apoptosis Detection kit. The level of proteins in the EGFR downstream pathway was observed using a western blot assay. The results showed that the cells with the EGFR‑sensitive mutation (HCC827, EGFR E716‑A750del) were more sensitive to icotinib compared with those possessing the EGFR wild‑type (A549) and the EGFR‑resistant mutations (H1650, EGFR E716‑A750del and PTEN lost; H1975, EGFR L858R+T790M). Quinalizarin inhibited proliferation and promoted apoptosis in the cells with the EGFR wild‑type and resistant mutations, and the addition of quinalizarin to icotinib partially restored their sensitivity to icotinib. Quinalizarin and/or icotinib increased the apoptotic rates in the EGFR‑TKI resistant cells, and the combination of these reduced the level of protein downstream of EGFR, including phosphorylated (p‑AKT) and p‑(ERK). In conclusion, quinalizarin may partially sensitize cells to icotinib by inhibiting proliferation and promoting apoptosis mediated by AKT and ERK in EGFR‑TKI resistant NSCLC cell lines.
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Copy and paste a formatted citation
Spandidos Publications style
Li K, Zhou F, Zhou Y, Zhang S, Li Q, Li Z, Liu L, Wu G and Meng R: Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines. Int J Mol Med 44: 437-446, 2019.
APA
Li, K., Zhou, F., Zhou, Y., Zhang, S., Li, Q., Li, Z. ... Meng, R. (2019). Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines. International Journal of Molecular Medicine, 44, 437-446. https://doi.org/10.3892/ijmm.2019.4220
MLA
Li, K., Zhou, F., Zhou, Y., Zhang, S., Li, Q., Li, Z., Liu, L., Wu, G., Meng, R."Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines". International Journal of Molecular Medicine 44.2 (2019): 437-446.
Chicago
Li, K., Zhou, F., Zhou, Y., Zhang, S., Li, Q., Li, Z., Liu, L., Wu, G., Meng, R."Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines". International Journal of Molecular Medicine 44, no. 2 (2019): 437-446. https://doi.org/10.3892/ijmm.2019.4220
Copy and paste a formatted citation
x
Spandidos Publications style
Li K, Zhou F, Zhou Y, Zhang S, Li Q, Li Z, Liu L, Wu G and Meng R: Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines. Int J Mol Med 44: 437-446, 2019.
APA
Li, K., Zhou, F., Zhou, Y., Zhang, S., Li, Q., Li, Z. ... Meng, R. (2019). Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines. International Journal of Molecular Medicine, 44, 437-446. https://doi.org/10.3892/ijmm.2019.4220
MLA
Li, K., Zhou, F., Zhou, Y., Zhang, S., Li, Q., Li, Z., Liu, L., Wu, G., Meng, R."Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines". International Journal of Molecular Medicine 44.2 (2019): 437-446.
Chicago
Li, K., Zhou, F., Zhou, Y., Zhang, S., Li, Q., Li, Z., Liu, L., Wu, G., Meng, R."Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines". International Journal of Molecular Medicine 44, no. 2 (2019): 437-446. https://doi.org/10.3892/ijmm.2019.4220
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