Fucoxanthin Inactivates the PI3K/Akt Signaling Pathway to Mediate Malignant Biological Behaviors of Non-Small Cell Lung Cancer

Abstract

Although lung cancer treatment strategies have improved in recent years, the 5-year overall survival of non-small cell lung cancer (NSCLC) remains less than 15%. Chemotherapy is considered the most promising option in the comprehensive treatment of NSCLC. Fucoxanthin (FX) is a natural product derived from brown algae and has extensive applications in medicine. Previous studies reported that FX effectively inhibits the growth of NSCLC cells in vitro and in vivo. However, the mechanism underlying the anti-NSCLC effect of FX remains unknown. In this study, NSCLC cell lines and a xenograft nude mouse model were used to examine the anti-NSCLC activities of FX in vitro and in vivo. Network pharmacology analysis and inhibitors or activators of the PI3K/Akt signaling pathway were used to explore the anti-NSCLC mechanisms of FX. The results indicated that FX could inhibit proliferation, migration, and invasion, arrest cell cycle at the G0/G1 phase, and induce apoptosis of NSCLC cells in vitro. Additionally, FX suppressed tumor growth in vivo. The PI3K/Akt signaling pathway was found to be involved in the anti-NSCLC activity of FX. In conclusion, FX inhibits malignant biological behaviors of NSCLC by suppressing the phosphorylation of both PI3K and AKT, and subsequently inactivating PI3K/AKT signaling pathway.

Acknowledgments

We appreciate the GO, Kyoto Encyclopedia of Genes and KEGG databases for providing open access.

Author Contributions

Conceptualization, X.F., H.Y. and Y.L.; methodology, Y.Z., T.Z.; software, X.F., T.Z., Q.L.; validation, X.L., D.J., L.F. and J.L.; formal analysis, X.F., Y.L.; investigation, Z. H.; resources, H.Y. and Y.L.; data curation, L. Z., J.W.; writing original draft preparation, X.F.; writing review and editing, Y.L.; visualization, H.Y.; supervision, Y.L., H.Y.; project administration, Y.L.; funding acquisition, H.Y. All authors have read and agreed to the published version of the manuscript.

Disclosure Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

This work was funded by Special Support Project for Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang) under Grant [ZJW-2019-007]; Science and Technology Innovation Project of Guangdong Province, China, Grants [2019A01005, 2019A03023]; and Discipline construction project of Guangdong Medical University, Grant [4SG21011G].

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Animal Experimental Ethics Committee of GDMU (protocol code GDY202090 and date of approval 2020. 03. 13).

Data Availability Statement

Data used in our research can be obtained in the GO, Kyoto Encyclopedia of Genes and KEGG.