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Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol
Xu S.-W.3; Law B.Y.K.3; Mok S.W.F.3; Leung E.L.H.3; Fan X.X.3; Coghi P.S.3; Zeng W.3; Leung C.-H.2; Ma D.-L.1; Liu L.3; Wong V.K.W.3
2016-10-01
Source PublicationInternational Journal of Oncology
ISSN17912423 10196439
Volume49Issue:4Pages:1576-1588
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.

KeywordAutophagy Calcium Celastrol Epidermal Growth Factor Receptor Gefitinib-resistant Lung Cancer
DOI10.3892/ijo.2016.3644
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000383311400034
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Cited Times [WOS]:12   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Hong Kong Baptist University
2.University of Macau
3.Macau University of Science and Technology
Recommended Citation
GB/T 7714
Xu S.-W.,Law B.Y.K.,Mok S.W.F.,et al. Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol[J]. International Journal of Oncology,2016,49(4):1576-1588.
APA Xu S.-W..,Law B.Y.K..,Mok S.W.F..,Leung E.L.H..,Fan X.X..,...&Wong V.K.W..(2016).Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol.International Journal of Oncology,49(4),1576-1588.
MLA Xu S.-W.,et al."Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol".International Journal of Oncology 49.4(2016):1576-1588.
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