Establishment of a patient-derived xenotransplantation model of gastric cancer and its application in pharmacodynamics study / 肿瘤研究与临床

ABSTRACT

Objective:To establish a patient-derived xenotransplantation (PDX) animal model of gastric cancer, and observe the anti-cancer effect of chemotherapeutic drugs on this model.Methods:Human gastric cancer tissues were inoculated into the subcutaneous tissues of both axillaries of NOG mice and were subcultured for 3 generations. The tumor tissues of the third-generation NOG mice were selected and inoculated into the subcutaneous tissues of left axillary of 21 severe combined immunodeficiency-non-obese diabetes mellitus (SCID-NOD) mice to establish PDX mouse model of gastric cancer. The inoculated mice were divided into control group (mice received only 0.9% sodium chloride injection), oxaliplatin group, cisplatin group, paclitaxel group, fluorouracil group, tegafur, gimeracil and oteracil porassium capsules group and capecitabine group, with 3 mice in each group, and the corresponding drugs were given. The mice survival status, tumor volume and tumor weight at different times were recorded. Mice were sacrificed on the 61st day of administration, and the tumor inhibition effects of 6 kinds of chemotherapy drugs on the PDX model of gastric cancer were evaluated.Results:After being subcultured for 3 generations, the stability of tumor transmission in PDX animal model of gastric cancer was improved, and the homogeneity of tumor growth was good at the initial stage. At the early stage of administration, the model was more sensitive to oxaliplatin, fluorouracil and capecitabine, and the tumor growth inhibition (TGI) values on the 31st day were 63.37%, 52.11% and 78.48%, at the end of administration, the model had the best sensitivity to capecitabine with a TGI value of 59.22% and a tumor inhibition rate of 58.65% on the 61st day. The TGI curve after administration showed that paclitaxel had no obvious anti-tumor effect, cisplatin had the worst anti-tumor effect, and the model had poor tolerance to tegafur, gimeracil and oteracil porassium capsules.Conclusion:The PDX animal model of gastric cancer is successfully established, and capecitabine has the best tumor suppressive effect on this model.