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Cordycepin Reverses Cisplatin Resistance in Non-Small Cell Lung Cancer by Activating AMPK and Inhibiting the AKT Signaling Pathway
lizhu lin
the First Affiliated Hospital,Guangzhou University of Chinese Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8283-6554
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Cisplatin (DDP) is the firs-line chemotherapeutic agent for the treatment of NSCLC. However, DDP resistance limits their usage to maximize the antineoplastic effect. The aims of this study were to investigate whether cordycepin (Cor) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms.
Methods: Cell proliferation and apoptosis were analyzed in NSCLC cell lines in vitro and in vivo, parental and DDP-resistant A549 cells, treated with DDP alone or combination with Cor. Proteins of different signaling pathways were investigated between DDP-sensistive and -insensitive A549 cell lines by GO terms and KEGG analysis, and perturbations of the MAPK and PI3K-AKT signaling pathways were evaluated by western blot.
Results: Our data showed that Cor enhanced DDP inhibition of cell proliferation and promotion of apoptosis markedly compared to DDP alone group in both A549 and A549DDP. The synergic actions were associated with activation of AMPK and inhibition of AKT, mTOR and downstream P709S6K, S6 phosphorylation in the AKT pathway.
Conclusion: Cor/DDP combination has synergistic effect on inhibiting proliferation and promoting apoptosis of NSCLC cells in the presence or absence of DDP resistance.
Keywords
NSCLC, Cisplatin, Resistance, Cordycepin, AMPK, AKT
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This is a preprint. It has not completed peer review.
Research
Cordycepin Reverses Cisplatin Resistance in Non-Small Cell Lung Cancer by Activating AMPK and Inhibiting the AKT Signaling Pathway
lizhu lin
the First Affiliated Hospital,Guangzhou University of Chinese Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8283-6554
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 23 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Cisplatin (DDP) is the firs-line chemotherapeutic agent for the treatment of NSCLC. However, DDP resistance limits their usage to maximize the antineoplastic effect. The aims of this study were to investigate whether cordycepin (Cor) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms.
Methods: Cell proliferation and apoptosis were analyzed in NSCLC cell lines in vitro and in vivo, parental and DDP-resistant A549 cells, treated with DDP alone or combination with Cor. Proteins of different signaling pathways were investigated between DDP-sensistive and -insensitive A549 cell lines by GO terms and KEGG analysis, and perturbations of the MAPK and PI3K-AKT signaling pathways were evaluated by western blot.
Results: Our data showed that Cor enhanced DDP inhibition of cell proliferation and promotion of apoptosis markedly compared to DDP alone group in both A549 and A549DDP. The synergic actions were associated with activation of AMPK and inhibition of AKT, mTOR and downstream P709S6K, S6 phosphorylation in the AKT pathway.
Conclusion: Cor/DDP combination has synergistic effect on inhibiting proliferation and promoting apoptosis of NSCLC cells in the presence or absence of DDP resistance.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8