Polyphyllin I inhibits growth and invasion of cisplatin-resistant gastric cancer cells by partially inhibiting CIP2A/PP2A/Akt signaling axis

Abstract

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.

Retracted: Amentoflavone Promotes Apoptosis in Non‐Small‐Cell Lung Cancer by Modulating Cancerous Inhibitor of PP2A

“…Apart from being involved in cancer cell growth and apoptosis, CIP2A has also been found to play a role in chemoresistance of a variety of cancer cells. Recently, it has been found that inhibition of CIP2A enhanced the sensitivity to cisplatin in bladder cancer, gastric cancer, and ovarian cancer cells (Gao et al, ; Zhang et al, ; Li et al, ). In addition, the involvement of CIP2A in regulating metastatic process has also been evidenced.…”

Polyphyllin I attenuates cognitive impairments and reduces AD‐like pathology through CIP2A‐PP2A signaling pathway in 3XTg‐AD mice

“…CIP2A is a specific inhibitor of PP2A which is the most important tau phosphatase, and PPI can inhibit the expression of CIP2A protein in tumor 35,36 . To investigate whether PPI dephosphorylates tau by inhibiting CIP2A expression, the CIP2A and tau co‐transfected HEK293‐T cells were incubated with or without PPI (0.125, 0.25, 0.5, 1.0, or 2.0 μM) incubation for 48 hours and with or without PPI (0.5 μM) incubation for 6, 12, 24, 48, or 72 hours, and CIP2A expression, PP2A activity, and tau phosphorylation were detected.…”

“…33,34 Recently several labs have shown that PPI can inhibit tumor progression by inhibiting the expression of CIP2A. 35,36 Whether PPI can modulate the CIP2A expression thus ameliorating AD-related pathologic changes in AD is worthy exploration and identification.…”

“…In addition, studies showed that PPI has preclinical anticancer effect in various types of cancer, 29‐32 by reducing cancer‐related symptoms as well as adverse drug reactions, and inhibiting tumor growth 33,34 . Recently several labs have shown that PPI can inhibit tumor progression by inhibiting the expression of CIP2A 35,36 . Whether PPI can modulate the CIP2A expression thus ameliorating AD‐related pathologic changes in AD is worthy exploration and identification.…”

“…53 Previous studies have shown that PPI can inhibit the expression of CIP2A and accelerate its decomposition, which suggests that PPI is an effective inhibitor of CIP2A. 35 CIP2A is an inhibitor of PP2A, and PPI can reactivate PP2A by inhibiting CIP2A. 36 Thus, we explored the effects of PPI both in cells and AD animal models.…”