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Article

Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol

  • Authors:
    • Su-Wei Xu
    • Betty Yuen Kwan Law
    • Simon Wing Fai Mok
    • Elaine Lai Han Leung
    • Xing Xing Fan
    • Paolo Saul Coghi
    • Wu Zeng
    • Chung-Hang Leung
    • Dik-Lung Ma
    • Liang Liu
    • Vincent Kam Wai Wong
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, P.R. China, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, P.R. China, Department of Chemistry, Hong Kong Baptist University, Hong Kong, P.R. China
  • Pages: 1576-1588
    |
    Published online on: August 3, 2016
       https://doi.org/10.3892/ijo.2016.3644
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Abstract

Drug resistance of non-small cell lung cancer (NSCLC) is highly correlated to the mutation of the epidermal growth factor receptor (EGFR). Although EGFR tyrosine kinase inhibitors (TKIs) are available clinically, the molecular complexity of NSCLC has made it necessary to search for alternative therapeutic approaches to overcome the drug resistance of NSCLC. In the present study, we identified a triterpene molecule derived from the herbal plant Tripterygium wilfordii, celastrol, as a novel autophagy inducer. We demonstrate that celastrol exhibited selective cytotoxic effect towards EGFR mutant NSCLCs. In addition, celastrol also facilitated the autophagic degradation of Hsp90 client protein including EGFR and Akt on both EGFR wild-type and mutant NSCLCs via calcium-mediated autophagy. Blockage of celastrol-induced autophagic degradation of EGFR by autophagic inhibitor or calcium chelator decreased celastrol-mediated cell death in gefitinib-resistant NSCLCs. Overall, our findings suggest that celastrol may be developed as an effective anticancer agent for treatment of gefitinib-resistant NSCLC in the future.
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Copy and paste a formatted citation
Spandidos Publications style
Xu S, Law BY, Mok SW, Leung EL, Fan XX, Coghi PS, Zeng W, Leung C, Ma D, Liu L, Liu L, et al: Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol. Int J Oncol 49: 1576-1588, 2016.
APA
Xu, S., Law, B.Y., Mok, S.W., Leung, E.L., Fan, X.X., Coghi, P.S. ... Wong, V.K. (2016). Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol. International Journal of Oncology, 49, 1576-1588. https://doi.org/10.3892/ijo.2016.3644
MLA
Xu, S., Law, B. Y., Mok, S. W., Leung, E. L., Fan, X. X., Coghi, P. S., Zeng, W., Leung, C., Ma, D., Liu, L., Wong, V. K."Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol". International Journal of Oncology 49.4 (2016): 1576-1588.
Chicago
Xu, S., Law, B. Y., Mok, S. W., Leung, E. L., Fan, X. X., Coghi, P. S., Zeng, W., Leung, C., Ma, D., Liu, L., Wong, V. K."Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol". International Journal of Oncology 49, no. 4 (2016): 1576-1588. https://doi.org/10.3892/ijo.2016.3644
Copy and paste a formatted citation
x
Spandidos Publications style
Xu S, Law BY, Mok SW, Leung EL, Fan XX, Coghi PS, Zeng W, Leung C, Ma D, Liu L, Liu L, et al: Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol. Int J Oncol 49: 1576-1588, 2016.
APA
Xu, S., Law, B.Y., Mok, S.W., Leung, E.L., Fan, X.X., Coghi, P.S. ... Wong, V.K. (2016). Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol. International Journal of Oncology, 49, 1576-1588. https://doi.org/10.3892/ijo.2016.3644
MLA
Xu, S., Law, B. Y., Mok, S. W., Leung, E. L., Fan, X. X., Coghi, P. S., Zeng, W., Leung, C., Ma, D., Liu, L., Wong, V. K."Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol". International Journal of Oncology 49.4 (2016): 1576-1588.
Chicago
Xu, S., Law, B. Y., Mok, S. W., Leung, E. L., Fan, X. X., Coghi, P. S., Zeng, W., Leung, C., Ma, D., Liu, L., Wong, V. K."Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol". International Journal of Oncology 49, no. 4 (2016): 1576-1588. https://doi.org/10.3892/ijo.2016.3644
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