Polyphyllin I and VII potentiate the chemosensitivity of A549/DDP cells to cisplatin by enhancing apoptosis, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis

Feng,Feifei; Cheng,Peng; Wang,Chaochao; Wang,Yongbin; Wang,Wei

doi:10.3892/ol.2019.10895

Polyphyllin I and VII potentiate the chemosensitivity of A549/DDP cells to cisplatin by enhancing apoptosis, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis

Authors:
- Feifei Feng
- Peng Cheng
- Chaochao Wang
- Yongbin Wang
- Wei Wang
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Affiliations: Department of Respiratory Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Neural Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
Published online on: September 20, 2019 https://doi.org/10.3892/ol.2019.10895
Pages: 5428-5436
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Poor response and resistance to cisplatin (DDP)‑based chemotherapy frequently leads to treatment failure in advanced non‑small cell lung cancer (NSCLC). The underlying molecular mechanism is extremely complex and currently remains unclear. The overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes the epithelial‑to‑mesenchymal transition (EMT) and metastasis. The EMT has been reported to promote drug resistance in numerous previous studies. CIP2A and its downstream protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway also plays a role in mediating DDP resistance. Polyphyllin I (PPI) and polyphyllin VII (PPVII) are natural components extracted from Paris polyphylla that display anti‑cancer properties. In the present study, the chemosensitizing effects of PPI and PPVII were investigated in the DDP‑resistant NSCLC cell line A549/DDP, as well as the underlying molecular mechanisms. The results demonstrated that PPI and PPVII could significantly inhibit cell proliferation and enhance the sensitivities of A549/DDP cells to DDP. When assessing the underlying molecular mechanism, it was revealed that PPI and PPVII enhanced DDP‑induced apoptosis in A549/DDP cells via p53 upregulation and the caspase‑dependent pathway. Furthermore, PPI and PPVII reversed the EMT and suppressed CIP2A and its downstream AKT/mTOR signaling cascade in A549/DDP cells. Overall, the results from the present study demonstrated that PPI and PPVII may function as chemosensitizers by enhancing apoptosis via the p53 pathway, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis, and the combination with DDP may be a promising strategy for the development of new therapeutic agents.

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