Daurinoline suppressed the migration and invasion of chemo-resistant human non-small cell lung cancer cells by reversing EMT and Notch-1 and sensitized the cells to Taxol

•Daurinoline restore the sensitivity of resistant NSCLC cells was firstly found.•Daurinoline inhibite the migration and invasion of resistant NSCLC cells.•The anti-proliferation and anti-metastasis effects are related to EMT and Notch1.•We firstly found that daurinoline sensitizes chemo-resistant NS...

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Published inEnvironmental toxicology and pharmacology Vol. 66; pp. 109 - 115
Main Authors Li, Dan-Dan, Qin, Xiao-Chun, Yang, Yue, Chu, Hai-Xiao, Li, Ruo-Lan, Ma, Ling-xiang, Ding, Huai-Wei, Zhao, Qing-Chun
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.02.2019
Elsevier Science Ltd
Subjects
Anticancer properties
Cancer
Cell proliferation
Chemosensitization
Cisplatin
Cytotoxicity
Daurinoline
EMT
Epirubicin
Lung cancer
Non-small cell lung cancer
Non-small cell lung carcinoma
Notch1 protein
Paclitaxel
Phenotypes
Taxol
Terfenadine
Tumors
Chemosensitization
EMT
Daurinoline
Non-small cell lung cancer
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Summary:•Daurinoline restore the sensitivity of resistant NSCLC cells was firstly found.•Daurinoline inhibite the migration and invasion of resistant NSCLC cells.•The anti-proliferation and anti-metastasis effects are related to EMT and Notch1.•We firstly found that daurinoline sensitizes chemo-resistant NSCLC cells to taxol. Non-small cell lung cancer (NSCLC) is one of the most common malignancies, and Taxol is a cornerstone in the treatment. However, taxol-resistance eventually limits the clinical effects and applications. Daurinoline could restore the sensitivity of resistant MCF-7/adr and KBv200 cells. Whereas, the effect of daurinoline on the chemo-resistant NSCLC cells and the mechanism has not been elucidated. In this study, daurinoline was firstly demonstrated that inhibited the proliferation, migration, invasion and EMT phenotype of chemo-resistant NSCLC cells. And these effects were associated with EMT and Notch-1 reversal. Moreover, daurinoline could significantly enhance the anti-tumor effect of Taxol rather than epirubicin, adriamycin and cisplatin. And the reverse fold (RF) value of daurinoline was greater than terfenadine reported before. There are little cytotoxic effects of daurinoline and its derivatives reported by L.W. Fu, et al. (2001). Therefore, daurinoline may be a potential anti-tumor agent or chemosensitizer for chemo-resistant NSCLC patients.
ISSN:1382-6689
1872-7077
DOI:10.1016/j.etap.2018.12.005