Ginsenoside Rg5 inhibits cancer cell migration by inhibiting the nuclear factor‑κB and erythropoietin‑producing hepatocellular receptor A2 signaling pathways

Song,Leixin; Yang,Fan; Wang,Zhengtao; Yang,Li; Zhou,Yue

doi:10.3892/ol.2021.12713

Ginsenoside Rg5 inhibits cancer cell migration by inhibiting the nuclear factor‑κB and erythropoietin‑producing hepatocellular receptor A2 signaling pathways

Authors:
- Leixin Song
- Fan Yang
- Zhengtao Wang
- Li Yang
- Yue Zhou
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Affiliations: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: April 8, 2021 https://doi.org/10.3892/ol.2021.12713
Article Number: 452

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Abstract

The majority of cancer‑associated deaths are caused by cancer metastasis, the first step of which is the acquisition of migratory ability by cancer cells. Therefore, the suppression of cancer cell migration represents a potential efficient strategy to inhibit cancer metastasis. Inflammation induces cancer cell migration through the activation of nuclear factor‑κB (NF‑κB), which is a transcription factor that serves a central role in inflammatory signaling. Recent studies have demonstrated that the phosphorylation of the receptor tyrosine kinase erythropoietin‑producing hepatocellular receptor A2 (EphA2) at S897 promotes cancer cell migration. Therefore, a compound with the ability to abolish these two factors may suppress cancer metastasis. In the present study, ginseng saponin ginsenoside Rg5 was found to inhibit the phosphorylation of NF‑κB and EphA2. Therefore, this study aimed to elucidate the molecular mechanisms of ginsenoside Rg5 and determine whether it inhibited cancer cell migration. The results demonstrated that ginsenoside Rg5 inhibited the activation of NF‑κB by suppressing its upstream kinase transforming growth factor β‑activated kinase 1 in TNF‑α treated HeLa or A549 cells compared with that in the untreated control group. Furthermore, ginsenoside Rg5 attenuated the expression of EphA2 by lysosomal degradation, which inhibited its phosphorylation. In addition, ginsenoside Rg5 suppressed inflammatory cytokine‑induced cancer cell migration. In conclusion, the results of the present study provided a scientific basis for the development of ginsenoside Rg5 as a potential antimetastatic drug.

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