Journal
CANCER CELL INTERNATIONAL
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12935-020-01658-1
Keywords
EGFR; NSCLC; Parthenolide; In vitro; In vivo
Categories
Funding
- Guangdong Medical University [B2019016]
- Administration of Traditional Chinese Medicine of Guangdong Province [20201180]
- Science and Technology Special Project of Zhanjiang [2019A01009]
- Natural Science Foundation of Guangdong Province [2016B030309002]
- Basic and Applied Basic Research Program of Guangdong Province [2019A1515110201, GDNRC[2020]038]
- Educational Commission of Guangdong Province [4SG20138G]
- Fund of Southern Marine Science and Engineering GuangdongLaboratory (Zhanjiang) [ZJW-2019-007]
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BackgroundEGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known.MethodsThe CCK8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model.ResultsIn this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway.ConclusionsTaken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.
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