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Combining use of phillyrin and autophagy blocker exerts suppressive effect on nasopharyngeal carcinoma cell malignancy and autophagy via AMPK/mTOR/p70s6k signaling pathway

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Abstract

Background

Nasopharyngeal carcinoma (NPC) is one of the malignant cancers in southern China. Phillyrin is a major active constituent extracted from Forsythia suspensa (Thunb.) and possesses anti-inflammatory and anti-tumor properties.

Objective

This study was conducted to clarify the functional role and mechanism of autophagy in the anti-tumor effects induced by phillyrin, as well as the combined effects of phillyrin and the autophagy inhibitor chloroquine (CQ).

Results

Phillyrin dose-dependently suppressed NPC cell viability, whereas promoted cell apoptosis. In addition, phillyrin induced autophagy in NPC cells by increasing Beclin-1 protein expression and LC3-II/I ratio as well as decreasing p62 protein level. Pathway analysis showed that phillyrin enhanced the phosphorylation levels of AMPK but inhibited the phosphorylation of mTOR and p70s6k. Furthermore, the combined use of phillyrin and CQ further suppressed CNE-1 cell viability and promoted cell apoptosis.

Conclusion

These findings indicate that inhibition of autophagy by CQ enhances phillyrin-mediated anti-tumor activity in vitro, which may provide a novel strategy to improving the anti-cancer efficacy of drug treatment.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors appreciate all the participants providing supports for this study.

Funding

The work was supported by Bengbu Medical College Natural Science Key Fund Funded Project (Approval No. 2020byzd142).

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Authors and Affiliations

Authors

Contributions

YX were the main designers of this study. YX, CJ, ZC, WY, and SG performed the experiments and analyzed the data. YX and CJ drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chengyi Jiang.

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Conflict of interest

Yajia Xu declares that he has no conflict of interest. Chengyi Jiang declares that he has no conflict of interest. Zhongqiang Cheng declares that he has no conflict of interest. Weige Yao declares that she has no conflict of interest. Sichen Ge declares that she has no conflict of interest.

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Our study did not require an ethical board approval, because it did not contain human or animal trials.

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Xu, Y., Jiang, C., Cheng, Z. et al. Combining use of phillyrin and autophagy blocker exerts suppressive effect on nasopharyngeal carcinoma cell malignancy and autophagy via AMPK/mTOR/p70s6k signaling pathway. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00374-x

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