Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China.
Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China; Biomedical Research Institute, Hubei University of Medicine, Shiyan, Hubei, 442000, China.
J Pharmacol Sci. 2018 Jul;137(3):305-312. doi: 10.1016/j.jphs.2018.07.008. Epub 2018 Jul 26.
The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular process that occurs during cancer progression and metastasis, has been reported to promote drug resistance in several previous studies. Consequently, ongoing research has been focused on exploring therapeutic options for preventing EMT to delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component extracted from Paris polyphylla that displays anti-cancer properties. In the present study, we investigated whether PPI can be used in the cisplatin (DDP)-resistant human gastric cancer cell line SGC7901/DDP. The results demonstrated that PPI treatment significantly inhibited cell proliferation, invasion and EMT. TGF-β1 is known to promote EMT-induced metastasis in numerous tumor types. PPI inhibited the invasion of TGFβ1-induced SGC7901/DDP cells in vitro. PPI also increased the mRNA and protein expression levels of E-cadherin but decreased the expression levels of vimentin. Further examination of the mechanism revealed that the CIP2A/PP2A/Akt pathway is partially involved in this regulation of EMT-related biomarkers and invasion. Furthermore, xenograft tests also confirmed the antitumor effects of PPI in vivo. We propose that PPI could be developed as a candidate drug for treating cancer invasion and migration.
癌性蛋白磷酸酶 2A 抑制剂（CIP2A）的异常表达预示着不良预后，并促进 EMT 和转移。EMT 是癌症进展和转移过程中的一个关键细胞过程，已有多项研究报道其促进了耐药性的产生。因此，目前的研究重点是探索预防 EMT 的治疗选择，以延迟或逆转耐药性。重楼苷 I（PPI）是从云南重楼中提取的一种天然成分，具有抗癌特性。在本研究中，我们研究了 PPI 是否可以用于顺铂（DDP）耐药的人胃癌细胞系 SGC7901/DDP。结果表明，PPI 处理显著抑制了细胞增殖、侵袭和 EMT。TGF-β1 被认为在多种肿瘤类型中促进 EMT 诱导的转移。PPI 抑制了 TGFβ1 诱导的 SGC7901/DDP 细胞在体外的侵袭。PPI 还增加了 E-钙粘蛋白的 mRNA 和蛋白表达水平，降低了波形蛋白的表达水平。进一步的机制研究表明，CIP2A/PP2A/Akt 通路部分参与了 EMT 相关生物标志物和侵袭的调节。此外，异种移植实验也证实了 PPI 在体内的抗肿瘤作用。我们提出，PPI 可以开发为治疗癌症侵袭和迁移的候选药物。
