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Fungal Immunomodulatory Protein from Nectria haematococca Suppresses Growth of Human Lung Adenocarcinoma by Inhibiting the PI3K/Akt Pathway

1
Laboratory of Food Enzyme Engineering, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China
2
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
3
University of Chinese Academy of Sciences, Beijing 100049, China
4
Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China
5
Guangzhou Baiyunshan Zhongyi Pharmaceutical Co., Ltd., Guangzhou 510530, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally in this work.
Int. J. Mol. Sci. 2018, 19(11), 3429; https://doi.org/10.3390/ijms19113429
Received: 17 October 2018 / Accepted: 30 October 2018 / Published: 1 November 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Lung cancer is a common disease that is associated with poor prognosis. Fungal immunomodulatory protein from Nectria haematococca (FIP-nha) has potential as a lung cancer therapeutic; as such, illuminating its anti-tumor mechanism is expected to facilitate novel treatment options. Here, we showed that FIP-nha affects lung adenocarcinoma growth ex vivo and in vivo. Comparative quantitative proteomics showed that FIP-nha negatively regulates PI3K/Akt signaling and induces cell cycle arrest, autophagy, and apoptosis. We further demonstrated that FIP-nha suppresses Akt phosphorylation, leading to upregulation of p21 and p27 and downregulation of cyclin B1, cyclin D1, CDK2, and CDK4 expression, ultimately resulting in G1/S and G2/M cell cycle arrest. Meanwhile, FIP-nha-induced PI3K/Akt downregulation promotes A549 apoptosis by increasing the expression ratio of Bax/Bcl-2 and c-PARP and autophagy by decreasing the phosphorylation of mTOR. Thus, we comprehensively revealed the anti-tumor mechanism of FIP-nha, which inhibits tumor growth by modulating PI3K/Akt-regulated cell cycle arrest, autophagy, and apoptosis, and provided the basis for further application of fungal immunomodulatory proteins, especially FIP-nha. View Full-Text
Keywords: fungal immunomodulatory protein; Nectria haematococca; lung adenocarcinoma; PI3K/Akt; apoptosis; autophagy; cell cycle arrest fungal immunomodulatory protein; Nectria haematococca; lung adenocarcinoma; PI3K/Akt; apoptosis; autophagy; cell cycle arrest
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Xie, Y.; Li, S.; Sun, L.; Liu, S.; Wang, F.; Wen, B.; Sun, L.; Fang, X.; Chai, Y.; Cao, H.; Jia, N.; Gu, T.; Lou, X.; Xin, F. Fungal Immunomodulatory Protein from Nectria haematococca Suppresses Growth of Human Lung Adenocarcinoma by Inhibiting the PI3K/Akt Pathway. Int. J. Mol. Sci. 2018, 19, 3429.

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