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ECB-ART-46730
Int J Mol Sci 2018 Nov 01;1911:. doi: 10.3390/ijms19113429.
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Fungal Immunomodulatory Protein from Nectria haematococca Suppresses Growth of Human Lung Adenocarcinoma by Inhibiting the PI3K/Akt Pathway.

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 .


Abstract
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.

PubMed ID: 30388826
PMC ID: PMC6274709
Article link: Int J Mol Sci
Grant support: [+]

Species referenced: Echinodermata
Genes referenced: bax cdk2 cdk6 LOC100893907 LOC115919910 LOC582192 LOC586734 LOC588766 LOC592256


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References [+] :
Cai, PI3K/AKT/mTOR signaling pathway inhibitors in proliferation of retinal pigment epithelial cells. 2012, Pubmed