ICG-001 Suppresses Growth Of Gastric Cancer Cells And Chemoresistance And The Role And Mechanism Of KIF23/MKLP1 In Initiation And Progress Of Gastric Cancer

Objective: ICG-001,a small molecular inhibitior of Wnt/?-catenin signaling pathway,has been proved to suppress cancer cell growth in many types of tumors.IC G-001 mainly interferes with the interaction of CBP with ?-catenin and inhibits the transcriptional activity of CBP through competitive ly binding of CREB-binding protein(C BP).KIF23(K inesin family 23)is one member of the kinesin family,encoding the mitogenic protein MKLP1,whose function is to regulate cytokinesis.In a variety of tumors,KIF23/MK LP1 is overexpressed.However,the role of IC G-001 and KIF23/MKLP1 in gastric cancer and their molecular mechanisms are not very clear.The purpose of this study is to investigate the effect and mechanism of IC G-001 on the growth of gastric cancer cells,and to research into the carcinogenic function of KIF23/MKLP1 on gastric cancer,and to further explore its molecular biological mechanism.Methods: 1.Cell biology methods,such as MTT,flow cytometry,colony formation assay,cell migration and invasion,were used to study the effects of ICG-001 on proliferation,migration and invasion,and apoptosis of gastric cancer cells.2.By inducing cancer stem-like cell population in vitro,the sensitivity of these cells to chemotherapeutic drugs and ICG-001 was analyzed.3.The effect of ICG-001 on the binding of ?-catenin and related proteins was analyzed by immunoprecipitatio n.4.We used GEO and TCGA database,real-time fluorescence quantitative PCR and immunohistochemistry to analyze and confirm the expression level of KIF23/MKLP1 in gastric cancer.And its correlation with the progression and prognosis of gastric cancer and related molecular mechanisms were further explored.Results: 1.ICG-001 can inhibit the growth,migration and invasion of gastric cancer cells and induce cell apoptosis.2.ICG-001 can improve the sensitivity of stem-like cell population to chemotherapeutic drugs.3.ICG-001 inhibits of cell growth through interferring the association between ?-catenin and other related proteins.4.KIF23/MKLP1 is highly expressed in gastric cancer and promotes cell growth through interacting with Amer1 to potentiate Wnt/?-catenin signaling pathway.Conclusions: This study shows that ICG-001 can inhibit the growth of gastric cancer cells and improve their sensitivity to chemotherapeutic drugs.Through the research on mechanism of ICG-001,we digged out KIF23/MK LP1 as an oncogene,promoting the initiation and development of gastric cancer,and its related molecular mechanisms were further exolored.This is of great theoretical significance not only for understanding the molecular mechanism of gastric cancer,but also for improving gastric cancer chemotherapy and developing combined drugs.