Abstract
The compounds derived from Traditional Chinese Medicines have shown various pharmacological activities with unique advantages, especially in the aspect of antitumor. Neferine (Nef), a natural compound, extracted from green seed embryos of Lotus (Nelumbo nucifera Gaertn.) also exerts antitumor effects on cancers. In this study, the effects and mechanisms of Nef on epithelial-to-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC) were evaluated. The results showed that Nef had the antitumor effects in vivo and in vitro. Nef significantly suppressed cell viability and induced apoptosis in NSCLC cells, with elevated reactive oxygen species and reduced BCL2/BAX ratio. Nef was also demonstrated to inhibit the invasion, metastasis and EMT process of NSCLC cells, and attenuate EMT-related changes of E-cadherin, N-cadherin and Vimentin at both transcriptional and translational levels. Moreover, we concluded that the inhibitory effects of Nef on EMT was achieved by targeting Rho-associated protein kinase 1, a protein mediating the process of EMT in various cancers. These results showed that Nef had a significant antitumor effect on NSCLC cells by inducing apoptosis and blocking EMT, providing the therapeutical prospect on NSCLC treatment.
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The datasets used during the present study are available from the corresponding author upon reasonable request.
Abbreviations
- ANOVA:
-
Analysis of variance
- BAX:
-
BCL2-associated X protein
- BCL2:
-
B-cell lymphoma-2
- DMSO:
-
Dimethyl sulfoxide
- ELISA:
-
Enzyme-linked immunosorbent assay
- EMT:
-
Epithelial-to-mesenchymal transition
- Fas:
-
Fasudil
- IC 50 :
-
Half maximal inhibitory concentration
- Nef:
-
Neferine
- NSCLC:
-
Non-small cell lung cancer
- OD:
-
Optical density
- PBS:
-
Phosphate-buffered saline
- qRT-qPCR:
-
Real-time quantitative polymerase chain reaction
- ROS:
-
Reactive oxygen species
- ROCK1:
-
Rho-associated protein kinase 1
- TCMs:
-
Traditional Chinese Medicines
- TGF-β1:
-
Transforming growth factor-β1
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Funding
Research supported by the National Natural Science Foundation of China (No. 81373295, 81473420); the Open Project of State Key Laboratory of Natural Medicines (No. SKLNMKF202202); the Natural Science Foundation of Jiangsu province (BK20220474); the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); and Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP).
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GY and YP conceived the idea; PH, PW and BY performed most of the research; QX and CL conducted the molecular docking; ZW, JX and SL analyzed the data; all authors contributed to the writing and revisions.
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Animal experiments were approved by the Review Board of Nanjing University of Chinese Medicine (Ethics number: 202011A002).
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Hu, P., Wan, P., Xu, A. et al. Neferine, a novel ROCK1-targeting inhibitor, blocks EMT process and induces apoptosis in non-small cell lung cancer. J Cancer Res Clin Oncol 149, 553–566 (2023). https://doi.org/10.1007/s00432-022-04280-y
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DOI: https://doi.org/10.1007/s00432-022-04280-y