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Abstract Title:

Ginsenoside Rg3 increases gemcitabine sensitivity of pancreatic adenocarcinoma via reducing ZFP91 mediated TSPYL2 destabilization.

Abstract Source:

J Ginseng Res. 2022 Sep ;46(5):636-645. Epub 2021 Aug 30. PMID: 36090681

Abstract Author(s):

Haixia Pan, Linhan Yang, Hansong Bai, Jing Luo, Ying Deng

Article Affiliation:

Haixia Pan

Abstract:

BACKGROUND: Ginsenoside Rg3 and gemcitabine have mutual enhancing antitumor effects. However, the underlying mechanisms are not clear. This study explored the influence of ginsenoside Rg3 on Zinc finger protein 91 homolog (ZFP91) expression in pancreatic adenocarcinoma (PAAD) and their regulatory mechanisms on gemcitabine sensitivity.

METHODS: RNA-seq and survival data from The Cancer Genome Atlas (TCGA)-PAAD and Genotype-Tissue Expression (GTEx) were used foranalysis. PANC-1, BxPC-3, and PANC-1 gemcitabine-resistant (PANC-1/GR) cells were used foranalysis. PANC-1 derived tumor xenograft nude mice model was used to assess the influence of ginsenoside Rg3 and ZFP91 on tumor growth.

RESULTS: Ginsenoside Rg3 reducedexpression in PAAD cells in a dose-dependent manner.upregulation was associated with significantly shorter survival of patients with PAAD.overexpression induced gemcitabine resistance, which was partly conquered by ginsenoside Rg3 treatment.depletion sensitized PANC-1/GR cells to gemcitabine treatment. ZFP91 interacted with Testis-Specific Y-Encoded-Like Protein 2 (TSPYL2), induced its poly-ubiquitination, and promoted proteasomal degradation. Ginsenoside Rg3 treatment weakened ZFP91-induced TSPYL2 poly-ubiquitination and degradation. Enforcedexpression increased gemcitabine sensitivity of PAAD cells and partly reversed induced gemcitabine resistance in PANC-1/GR cells.

CONCLUSION: Ginsenoside Rg3 can increase gemcitabine sensitivity of pancreatic adenocarcinoma at least via reducing ZFP91 mediated TSPYL2 destabilization.

Study Type : In Vitro Study

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