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

International Journal of Molecular Sciences

Xiangdong Fang¹  Lei Sun¹  Xiaomin Lou¹  Yushuang Chai²  Tianyi Gu³  Fengjiao Xin³  Shujun Liu³  Ning Jia³  Yingying Xie³  Shuying Li³  Hao Cao³  Lichao Sun³  Boting Wen³  Fengzhong Wang³ 

[1] CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;Guangzhou Baiyunshan Zhongyi Pharmaceutical Co., Ltd., Guangzhou 510530, China;Laboratory of Food Enzyme Engineering, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China;

关键词: fungal immunomodulatory protein;    Nectria haematococca;    lung adenocarcinoma;    PI3K/Akt;    apoptosis;    autophagy;    cell cycle arrest;   

DOI  :  10.3390/ijms19113429

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown