Estalishment And Pharmacodynamic Evaluation Of Patient Derived Gastric Cancer Cell Line

As a common malignant tumor of the digestive tract,the incidence and mortality rate of gastric cancer are relatively high.In China,the incidence of gastric cancer has a clear geographical distribution characteristic,especially in Jiangsu,Zhejiang and other places for the high incidence area.Due to the reasons of complex etiology,tumor heterogeneity and tumor resistance,the clinical effective treatment of gastric cancer is relatively low.Traditional gastric cancer cell lines have undergone more frequent subculture in vitro and happened gene transfer,this phenomenon lead to some changes in the biological characteristics of tumor cells,so these cells cannot fully reflect the clinical characteristics of the tumor;Moreover,The cell lines which can successfully establish mouse cancer xenograft models are very limited,so establishing new gastric cancer cell lines is very urgent.Firstly,we established gastric cancer PDX model which high correlate with clinical gastric cancer patients,and then used the transplanted tumor tissue to establish the corresponding human gastric cancer cell line,this method can not only improve the drug screening platform in vivo and in vitro to achieve the guidance of clinical individual treatment,but also provide important experimental materials for gastric cancer related research.We used the clinical gastric cancer tissue to establish gastric cancer PDX model,then selected 12 gastric cancer PDX model from the establishment model library,6 gastric cancer cell lines were successfully established after the original tissue culture in vitro,these cell lines were named GAXC-001,GAXC-023,GAXC-031,GAXC-036,GAXC-066 and GAXC-150.These cell lines grow stably and passaged in vitro.Thebiological characteristics of these cell lines were identified by cell morphological observation,in vitro growth kinetics,karyotype analysis,STR identification,immunohistochemistry and in vivo tumorigenesis experiments.The results showed that the traits of these cell lines were stable.The number and structure of chromosomes were all distorted seriously,which accorded with the genetic characteristics of malignant tumors.Compared with the parental PDX model,these cell lines have the main clinical biological characteristics;also have high tumorigenicity,short incubation period,high tumor formation rate and uniformity.In order to achieve the goal of guiding the gastric cancer clinical drug use,we chose the more classic gastric cancer clinical treatment chemotherapy drugs for the in vitro drug sensitivity research of the cell line,and use 5-Fu and cisplatin to study the pharmacodynamics in vivo on the cell line and its corresponding parental PDX model,and then analyzed the correlation between in vivo and in vitro drug sensitivity test data.The results showed that there was a significant difference in different tumor models with the same chemotherapy drug.There was a high correlation in the data of in vivo,in vitro and the corresponding PDX model on the same chemotherapy drug;GAXC-023 transplanted tumor in vivo has natural resistance to cisplatin and GAXC-066 has natural resistance to 5-Fu.In summary,the cell lines established in this study were stable and retained most of the biological characteristics of clinical gastric cancer patient tumor tissue.These cell lines and their associated models can be used for the development of gastric anti-cancer drugs and the basic research of tumors,in which resistant cell lines can be used in the study of gastric cancer resistance mechanisms.