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Short-term Efficacy Evaluation And Its Mechanism Of Shenqiyizhu Decoction Combined Chemotherapy In The Treatment Of Advanced Gastric Cancer

Posted on:2018-10-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:J L XuFull Text:PDF
GTID:1314330515967699Subject:Internal medicine of traditional Chinese medicine
Abstract/Summary:PDF Full Text Request
Objective This study was to investigate the effect of Shenqiyizhu Decoction combined with chemotherapy on the short-term clinical efficacy and clinical benefit of patients with advanced gastric cancer.And this study was also to study the mechanism of Shenqiyizhu Decoction in the treatment of gastric cancer,provide the basis for the clinical treatment of gastric cancer with Traditional Chinese Medicine,and to lay the foundation for the development of new drugs for gastric cancer,through observing the effect of Shenqiyizhu Decoction on the proliferation of gastric cancer SGC-7901 cells and epithelial-mesenchymal transition of these cells through Wnt/?-catenin signaling pathway.Methods ?62 cases of patients with advanced gastric cancer were randomly divided into observation group and control group(31 cases in each group).The patients in control group received chemotherapy(Tegafur Gimeracil Otera 80mg/m2/d + oxaliplatin 130mg/m2),while the observation group received Shenqiyizhu Decoction(300mL/time,twice a day)in addition to the chemotherapy same in the control group.The clinical efficacy,tumor marker level,immune function index,vascular endothelial growth factor(VEGF)level were observed before and after the treatment.?The gastric cancer SGC-7901 cells were treated with different concentrations of Shenqiyizhu Decoction(7.2g/100g/d,3.6g/100g/d,1.8g/100g/d,0.9g/100g/d)for 24 hours,then MTT assay was used to detect the cell growth and the changes of cell growth were observed.Gastric cancer SGC-7901 cells were cultured with NaCl(20 mmol/L),LiCl(20 mmol/L),LiCl(20 mmol/L)+ Shenqiyizhu Decoction containing serum(low dose),LiCl(20mmol/L)+ Shenqiyizhu Decoction containing serum(Middle dose),and LiCl(20mmol/L)?Shenqiyizhu Decoction containing serum(high dose)in for 24 hours,and the cells were observed under electron microscope.The number of invasive cells in SGC-7901 cells was observed and counted by Transwell assay.The expression of ?-Gsk3?,?-catenin and Vimentin were detected by Western blot.Results ?The objective response rate and disease control rate were 61.29%and 84.85%in the observation group,which were significantly higher than those in the control group(48.39%,74.19%,P<0.05).The levels of tumor markers(CA125,CA199,CA242,CEA),immune function index(Treg%,Th17%,Th17/Treg ratio)and VEGF level in the observation group were significantly lower than those in the control group,while KPS score and comprehensive benefit rate were significantly higher than the control group(P<0.05).The bone marrow suppression,gastrointestinal reaction and peripheral nerve toxicity of the observation group were significantly lower than those of the control group(P<0.05).?The proliferation of SGC-7901 cells was not significantly inhibited at a dose of no more than 3.6g/100g/d of Shenqiyizhu Decoction(compared with the control group,P= 0.069),while the proliferation was significantly inhibited at a dose greater than 7.2 g/100 g/d(compared with the control group,P= 0.0068).The morphology of SGC-7901 was significantly changed from epithelial type to interstitial transformation after stimulation by LiCl for 24h.The low dose of Shenqiyizhu Decoction can not reverse the trend of cell epithelial transformation.With the increase of serum dose,the medium dose and high dose can gradually reverse the transformation of epithelial mesenchymal phenomenon.The invasion of SGC-7901 was significantly promoted after stimulation by LiCl for 24h,and cells pass through the Transwell hole significantly increased.The low dose of Shenqiyizhu Decoction can not reverse the trend of cell invasion.With the increase of serum dose,the medium dose and high dose can gradually reverse the invasion phenomenon.The number of cells passing through the Transwell wells was significantly decreased after treatment of medium and high dose of Shenqiyizhu Decoction containing serum(compared with LiCl,P=0.0189 and 0.0002,respectively).After 24h stimulation with LiCl,the wnt signaling pathway of SGC-7901 was stimulated,and the expression of p-Gsk3? and the transformation of cell epithelium was promoted,then the expression of ?-catenin and Vimentin was up-regulated.The expression of p-Gsk3?,?-catenin and Vimentin protein was significantly inhibited by medium and high dose of Shenqiyizhu Decoction containing serum.Conclusions The clinical part of this study shows that Shenqiyizhu Decoction combined with chemotherapy can improve the short-term efficacy of patients with advanced gastric cancer.Shenqiyizhu Decoction can reduce the toxicity of chemotherapy and improve clinical benefits,while it can also reduce the VEGF,enhance immunity.It is worth of reference for clinical promotion.The experimental part of this study shows that Shenqiyizhu Decoction containing serum can inhibit proliferation of gastric cancer SGC-7901 cells.Shenqiyizhu Decoction may inhibit the transformation and invasion and metastasis of gastric cancer cells by inhibiting Wnt/?-catenin signaling pathway,which may be one of the mechanisms for the treatment of gastric cancer and deserve further study.
Keywords/Search Tags:Stomach cancer, Shenqiyizhu decoction, Wnt/?-catenin signaling pathway, Epithelial mesenchymal transdifferentiation, efficacy, clinical benefit
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