Bufalin down-regulates Axl expression to inhibit cell proliferation and induce apoptosis in non-small-cell lung cancer cells.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Bufanolides
/ pharmacology
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Down-Regulation
/ drug effects
Drug Screening Assays, Antitumor
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Knockdown Techniques
Humans
Lung Neoplasms
/ drug therapy
Proto-Oncogene Proteins
/ antagonists & inhibitors
RNA, Small Interfering
/ metabolism
Receptor Protein-Tyrosine Kinases
/ antagonists & inhibitors
Transcription, Genetic
/ drug effects
Axl Receptor Tyrosine Kinase
Axl
Bufalin
NSCLC
apoptosis
Journal
Bioscience reports
ISSN: 1573-4935
Titre abrégé: Biosci Rep
Pays: England
ID NLM: 8102797
Informations de publication
Date de publication:
30 04 2020
30 04 2020
Historique:
received:
22
11
2019
revised:
16
03
2020
accepted:
26
03
2020
pubmed:
29
3
2020
medline:
30
3
2021
entrez:
29
3
2020
Statut:
ppublish
Résumé
Axl, a member of the TAM (Tyro3, AXL, Mer) receptor tyrosine kinase family, plays critical roles in cell growth, proliferation, apoptosis, and migration. In the present study, we demonstrated that the anti-cancer activity of bufalin, a major bioactive component of the Chinese traditional medicine Chan Su, is mediated by the down-regulation of Axl in non-small-cell lung cancer (NSCLC) cells. We observed the inhibitory effect of bufalin on the proliferation of A549 and H460 NSCLC cells and the clonogenicity of these cells was reduced by bufalin treatment in a dose-dependent manner. Next, we found that the protein level of Axl was decreased in proportion to the concentration of bufalin in both A549 and H460 cells. Moreover, the promoter activity of the Axl gene was decreased by bufalin in a dose- and time-dependent manner, indicating that bufalin down-regulates Axl gene expression at the transcriptional level. We further examined if the anti-proliferative property of bufalin is influenced by Axl at the protein level. Axl overexpression attenuated the effect of bufalin in inhibiting cell proliferation and colony formation and inducing apoptosis in H460 cells, while knockdown of Axl gene expression induced the opposite effect. Taken together, our data indicate that the anti-proliferative and pro-apoptotic effects of bufalin were associated with the protein level of Axl, suggesting that Axl is a potent therapeutic target of bufalin in suppressing proliferation and inducing apoptosis in NSCLC cells.
Identifiants
pubmed: 32219334
pii: 222485
doi: 10.1042/BSR20193959
pmc: PMC7146032
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Bufanolides
0
Proto-Oncogene Proteins
0
RNA, Small Interfering
0
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
bufalin
U549S98QLW
Axl Receptor Tyrosine Kinase
0
AXL protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 The Author(s).
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