The Anticancer Effect And Mechanism Of THZ2 In The Gastric Cancer

Objective:As a new small molecule inhibitor of CDK7,THZ2 has a good inhibitory effect on three negative breast cancer,but the anticancer effect on gastric cancer is unknown.The purpose of this experiment is to study the anticancer effect of THZ2 on gastric cancer and its mechanism.Method:Rlanguage was used to analyze the mRNA level of cancerous tissue and normal gastric tissue of gastric cancer?STAD?patients in TCGA database.The copy number of other genes of cancer tissue of STAD and the survival curve of STAD were analyzed.MTT assay was used to detect the proliferation of gastric cancer cells.Flow cytometry was used to detect the cell cycle distribution and apoptosis.DHE staining was used to detect the reactive oxygen species?ROS?in the cells.The expressions of cell cycle and apoptosis-related protein were detected by Western blot,and the xenotransplantation tumor experiment in nude mice with Balb/c was carried out to explore the anti-gastric cancer effect of THZ2 in vivo.Results:1.The level of CDK7 mRNA in cancerous tissue was higher than that in normal tissue.2.The survival time of patients with low expression of CDK7 mRNA was longer than that of patients with high expression of CDK7 mRNA in patients with low expression of p53 mRNA in TCGA data.3.THZ2 could inhibit the proliferation of many gastric cancer cells in vitro,and the IC₅₀ value was positively correlated with the expression level of CDK7protein.4.THZ2 could block the cell cycle in G₂/M phase of gastric cancer cells.5.THZ2 could induce apoptosis of gastric cancer cells and lead to increase in intracellular ROS level.NAC could partially reverse intracellular ROS level and apoptosis.6.The growth of BGC-823 xenografts was inhibited by THZ2.Conclusion:THZ2 could inhibit the growth of gastric cancer cells in vivo and in vitro.