Inhibitory effects of polyphyllins I and VII on human cisplatin-resistant NSCLC via p53 upregulation and CIP2A/AKT/mTOR signaling axis inhibition  

作　　者：FENG Fei-Fei CHENG Peng SUN Chao WANG Hui WANG Wei 

机构地区：[1]Department of Respiratory Medicine,The Second Hospital of Shandong University,Jinan 250033,China [2]Department of Neural Medicine,The Second Hospital of Shandong University,Jinan 250033,China [3]Department of Central Laboratory,The Second Hospital of Shandong University,Jinan 250033,China

出　　处：《Chinese Journal of Natural Medicines》2019年第10期768-777,共10页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81473485);the Natural Science Foundation of Shandong Province(No.2014ZRE27321)

摘　　要：Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and m TORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/m TOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I(PPI) and polyphyllin VII(PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin(DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/m TOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of m TOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and m TORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/m TOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I(PPI) and polyphyllin VII(PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin(DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/m TOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of m TOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.

关 键 词：POLYPHYLLIN I POLYPHYLLIN VII Cisplatin-resistance Non-small cell lung cancer P53 Cancerous inhibitor of protein phosphatase 2A 

分 类 号：R965[医药卫生—药理学]