Inhibitory effects of polyphyllins I and VII on human cisplatin-resistant NSCLC via p53 upregulation and CIP2A/AKT/mTOR signaling axis inhibition.
10.1016/S1875-5364(19)30093-7
- Author:
Fei-Fei FENG
1
;
Peng CHENG
2
;
Chao SUN
3
;
Hui WANG
1
;
Wei WANG
4
Author Information
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.
4. Department of Respiratory Medicine, The Second Hospital of Shandong University, Jinan 250033, China. Electronic address: sducp@qq.com.
- Publication Type:Journal Article
- Keywords:
Cancerous inhibitor of protein phosphatase 2A;
Cisplatin-resistance;
Non-small cell lung cancer;
Polyphyllin I;
Polyphyllin VII;
p53
- From:
Chinese Journal of Natural Medicines (English Ed.)
2019;17(10):768-777
- CountryChina
- Language:English
-
Abstract:
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 mTORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/mTOR 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/mTOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of mTOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.
