机构：[1]Cancer Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院[2]Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院[3]Outpatient Department, Chengdu Aurora Huan Hua Xiang, Chengdu, China[4]Department of Radiation Oncology, School of Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China四川省肿瘤医院
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 for in-silicon analysis. PANC-1, BxPC-3, and PANC-1 gemcitabine-resistant (PANC-1/GR) cells were used for in vitro analysis. PANC-1 derived tumor xenograft nude mice model was used to assess the influence of ginsenoside Rg3 and ZFP91 on tumor growth in vivo. Results Ginsenoside Rg3 reduced ZFP91 expression in PAAD cells in a dose-dependent manner. ZFP91 upregulation was associated with significantly shorter survival of patients with PAAD. ZFP91 overexpression induced gemcitabine resistance, which was partly conquered by ginsenoside Rg3 treatment. ZFP91 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. Enforced TSPYL2 expression 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. (c) 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|2 区医学
小类|1 区全科医学与补充医学1 区药物化学
最新[2023]版：
大类|2 区医学
小类|1 区药物化学1 区全科医学与补充医学
JCR分区：
出版当年[2022]版：
Q1CHEMISTRY, MEDICINALQ1INTEGRATIVE & COMPLEMENTARY MEDICINE
最新[2023]版：
Q1CHEMISTRY, MEDICINALQ1INTEGRATIVE & COMPLEMENTARY MEDICINE
第一作者机构：[1]Cancer Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
共同第一作者：
通讯作者：
通讯机构：[1]Cancer Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China[2]Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China[*1]Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.[*2]Cancer Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
推荐引用方式(GB/T 7714)：
Pan Haixia,Yang Linhan,Bai Hansong,et al.Ginsenoside Rg3 increases gemcitabine sensitivity of pancreatic adenocarcinoma via reducing ZFP91 mediated TSPYL2 destabilization[J].JOURNAL OF GINSENG RESEARCH.2022,46(5):636-645.doi:10.1016/j.jgr.2021.08.004.
APA：
Pan, Haixia,Yang, Linhan,Bai, Hansong,Luo, Jing&Deng, Ying.(2022).Ginsenoside Rg3 increases gemcitabine sensitivity of pancreatic adenocarcinoma via reducing ZFP91 mediated TSPYL2 destabilization.JOURNAL OF GINSENG RESEARCH,46,(5)
MLA：
Pan, Haixia,et al."Ginsenoside Rg3 increases gemcitabine sensitivity of pancreatic adenocarcinoma via reducing ZFP91 mediated TSPYL2 destabilization".JOURNAL OF GINSENG RESEARCH 46..5(2022):636-645
