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 partici...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.展开更多
基金supported by the National Natural Science Foundation of China(No.81473485)the Natural Science Foundation of Shandong Province(No.2014ZRE27321)
文摘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.
