Journal Article

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

Cao, Hao, Xie, Yingying, Xin, Fengjiao, Wang, Fengzhong, Wen, Boting, Chai, Yushuang, Li, Shuying, Sun, Lichao, Lou, Xiaomin, Liu, Shujun, Jia, Ning, Gu, Tianyi, Sun, Lei, Fang, Xiangdong

2018

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Apoptosis / Autophagy / Cancer therapies / Cell cycle / Cell growth / Drug dosages / Flow cytometry / Functional foods & nutraceuticals / Immunomodulators / Lung cancer / Natural products / Peptides / Phase transitions / Protein expression / Proteins