Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via CIP2A/PP2A/ERK signaling in prostate cancer

Polyphyllin I (PPI) is a natural compound extracted from the rhizomes of Paris polyphylla and has been used to treat fevers and headaches in China. In the present study, the antitumor activity of PPI in prostate cancer (PC) cells was evaluated. At low doses, PPI decreased proliferation, invasion and epithelial-mesenchymal transition (EMT) in PC cells. PPI decreased the expression of matrix metalloproteinase 7 (MMP7), an enzyme that is critical for tumor metastasis. PPI also decreased the expression of Snail and vimentin, which are EMT-associated factors. Additionally, PPI suppressed AP-1 transcriptional activity and AP-1 binding to the MMP7 and vimentin promoters. The results demonstrated that PPI downregulated the phosphorylation of extracellular signaling‑related kinase (ERK), which is upstream modulator of AP-1. The results of the present study demonstrated that PPI may inhibit the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/ERK axis, downregulate the expression of MMP7, vimentin, and Snail, and suppress tumor invasion and EMT. A PC xenograft mouse model was employed and the results revealed that PPI may decrease tumor growth and weight. Additionally, PPI may inhibit proliferating cell nuclear antigen expression and CIP2A/PP2A/ERK signaling pathway in PPI-treated tumors. Therefore, the results of the present study suggest that PPI may suppress the growth, invasion and EMT of PC cells via inhibition of CIP2A/PP2A/ERK signaling axis. As a result, PPI may be a novel target for the treatment of PC.

International journal of oncology. 2018 Jun 29 [Epub ahead of print]

Xuewen Liu, Zhiting Sun, Dandan Li, Jikun Deng, Jun Liu, Kaihuai Ma, Shanshan Qin, Yuan Si, Te Zhang, Tingting Feng, Ying Liu, Yan Tan

School of Basic Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China., Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China., School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

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