Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma  

作　　者：Linlin Qu Yannan Liu Jianjun Deng Xiaoxuan Ma Daidi Fan 

机构地区：[1]Shaanxi Key Laboratory of Degradable Biomedical Materials,School of Chemical Engineering,Northwest University,Xi'an,710069,China [2]Shaanxi R&D Centerof Biomaterials and Fermentation Engineering,Schoolof Chemical Engineering,Northwest University,Xi'an,710069,China [3]Biotech.&Biomed.Research Institute,Northwest University,Xi'an,710069,China [4]Xi'an Giant Biotechnology Co.,Ltd.,Xi'an,710076,China

出　　处：《Journal of Pharmaceutical Analysis》2023年第5期463-482,共20页药物分析学报（英文版）

基　　金：supported by the National Key R&D Program of China(Grant No.:2021YFC2101500);the National Natural Science Foundation of China(Grant Nos.:22078264,21978235,22108224,and 21978236);the Natural Science Basic Research Program of Shaanxi,China(Grant Nos.:2023-JC-JQ-17 and 2023-JCQN-0109);the Xi'an Science and Technology Project,China(Project No.:20191422315KYPT014JC016);Key Research and Development Program of Shaanxi,China(Grant No.:2022ZDLSF05-12).

摘　　要：Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.

关 键 词：Hepatocellular carcinoma Ginsenoside Rk3 APOPTOSIS AUTOPHAGY PI3K/AKT pathway 

分 类 号：R96[医药卫生—药理学]