The Anti-Gastric Adenocarcinoma Cancer Effects And Mechanisms Of Ginsenoside Rh4

Gastric adenocarcinoma(GAC)is classified as a common pathological type of gastric cancer,which accounts for about 90% of gastric malignancies.Due to the low early diagnosis rate of gastric adenocarcinoma,most patients have missed the best treatment time when diagnosed,resulting in the high mortality rate of gastric adenocarcinoma.At present,the main methods for treatment of gastric adenocarcinoma are surgery,but surgical treatment has high risk and great harm to human body.Therefore,it is urgent to develop efficient and safe therapeutic drugs.The rare ginsenoside Rh4 is a triol type rare saponin derived from the original ginseng triol group saponin.It has many pharmacological effects,such as anti-tumor,anti-inflammatory,antidiabetic,etc.which are better than the common ginsenosides.Studies have been proved that ginsenoside Rh4 has obvious inhibitory effect on the metastasis of various tumors,but few studies have involved the treatment of gastric adenocarcinoma by Rh4.Therefore,this subject explores the effects of ginsenoside Rh4 on the growth and metastasis of gastric adenocarcinoma from the aspects of proliferation,migration,invasion,epithelial mesenchymal transition(EMT)and signaling pathways of gastric adenocarcinoma cells through relevant experiments in vivo and in vitro.The specific experimental contents are as follows:1.Isolation and purification of rare ginsenoside Rh4 monomer.The mixture of ginsenoside was separated and purified by macroporous adsorption resin and preparative high performance liquid chromatography.The final product was ginsenoside Rh4 monomer with purity of 98.7%by analytical high performance liquid chromatography.2.Effects of ginsenoside Rh4 on the activity,proliferation and colony forming ability of gastric adenocarcinoma cell lines HGC-27 and BGC-823.Cytotoxicity assay,acridine orange/ethidium bromide(AO/EB)staining and cell cloning assay showed that ginsenoside RH4 inhibited the activity,proliferation,and colony formation of HGC-27 and BGC-823 cells in a dose-dependent manner.3.Effect of ginsenoside Rh4 on the metastasis of HGC-27 and BGC-823 cells.The results of cell scratch assay,Transwell assay,Western blot assay,real-time fluorescence quantitative PCR(q RT-PCR)and immunofluorescence assay showed that ginsenoside RH4 inhibited the metastasis of gastric adenocarcinoma cells in a dose-dependent manner.4.Anti gastric adenocarcinoma effect of ginsenoside Rh4 in vivo.An animal model of caudal vein pulmonary metastasis was established to evaluate the anti-gastric adenocarcinoma effect and safety of ginsenoside Rh4 in vivo.The results showed that ginsenoside Rh4 inhibited the growth and metastasis of gastric adenocarcinoma in mice in a dose-dependent manner.5.Mechanism of ginsenoside Rh4 against metastasis of gastric adenocarcinoma.The mechanism of ginsenoside Rh4 against gastric adenocarcinoma metastasis was explored by proteomics assay,SIX1-si RNA transfection assay and inhibitor assay.The results showed that ginsenoside Rh4 inhibited the metastasis of gastric adenocarcinoma by targeting SIX1 to regulate TGF-β/Smad2/3 signal pathway and reversing EMT process.In conclusion,this study clarified that ginsenoside RH4 regulates TGF-β/Smad2/3 signal pathway by targeting SIX1,reverses the process of cell EMT process,thus plays a role in inhibiting the metastasis of gastric adenocarcinoma,and provides a basis for the clinical use of ginsenoside Rh4.