Establishment Of Human Gastric Cancer Model In Nude Mice And Pathological Investigation

BackgroundGastric cancer is a common malignant disease of the digestive tract. In recent years its global morbidity and mortality showed an increasing trend. Establishment of animal models of gastric cancer is essential for the research on this disease. Human tumor cell lines transplanted into immune-deficient nude mice to establish the human xenograft tumor models have been widely used for preclinical evaluation of anti-cancer drug efficacy. But this model has many shortcomings, such as its ability to grow in mice and just a limited number of tumor models were established from the tumor cell lines, and tumor taking rate from tumor cell line transplant is low. There are also significant differences in biological characteristics between tumor cell line derived models and the patients primary tumor models. In order to better undestanding the pathogenesis and study preventio and treatment of gastric cancer, establishing a stable, reliable, and suitable animal model is very necessary.Research purposes1. Animal model of nude mice subcutaneously bearing human gastric cancer provides a reliable animal model to individualized treatment for patients with gastric cancer, and new drugs development and its related study.2. Investigate relationships between tumor transplantation successful rate and patients’gender, age, tumor histology type, clinical stage.3. Establish the gastric tumor models from the gastric cancer cell lines and compare their histopathology with the tumor models derived from patients’primary tumors to observe which kind of the model is closer to patient’s original tumors.Methods:1.Use human gastric cancer specimens to establish the tumor models in nude mice: fresh gastric tumor specimens collected from the local hospitals, the tumor block was trimmed into approximately2-3mm3,then use trocar needle to inject the tumor pieces subcutaneously into the flanks of BALB/c nude mice. The male patient’s tumor tissue is inoculated into the male nude mice and the female patient’s tumor is inoculation into the female nude mice. When the tumor size of the first generation tumor-bearing mice reached to500mm3, we removed the tumor, then soaked part of the specimens in4%paraformaldehyde fixation for pathologic examination and another part of the specimens were transplanted into the nude mice flanks subcutaneously to make second generation, and so on until the fifth generation. For each generation we observed the activity status of tumor-bearing mice, its ability to respond, the tumor growth status, and xenograft tumor histopathological changes.2. Observed the successfully transplanted tumors grown in nude mice and to calculate the tumor taking rate, then usd SPSS11.0statistical software to analyze data and compare the transplantation succesful rate with the patients’gender, age, tumor histology type, and clinical stage.3. Used tgastric tumor cell lines to establish nude mouse subcutaneous tumor models: The gastric cancer cell lines BGC823, MGC803and NC187were inoculated subcutaneously in the nude mice.Observed the tumor growth and then after killing the mice we took out tumor tissues to do the pathological examination. Compared the two kinds of methods established from cell lines and patients’primary tumors; discuss which kind of model is closer to the patients’original tumors.Results:1. Total of56fresh tumor specimens from gastric cancer patients were inoculated subcutaneously in the Balb/c nude mice, among them17tumors have hve grown in the nude mice; the tumor taking rate is30.4%. The tumor taking has no significant relationship with the patients’gender, age, tumor histology type, and clinical stage.2. Tumor growth curve was a linear growth and tumor size was uniform among the established models.3. Comparison of the histopathology of patients’tumor derived models and the gastric cancer cell lines derived models (HE staining and immunohistochemical staining of Ki67protein expression), the patients’tumor models are more mimic of patients’ original tumors than cell lines established models. Conclusion:Successfully established gastric cancer patients’primary tumor models in the nude mice retain most of the histopathological morphology of patients’original primary tumors.The patients’primary tumor models can provide reliable animal models for the study on the molecular biology, genemics, and selection of new anticancer agents for the treatment of gastric cancer.