The Role Of Palmitoyltransferase ZDHHC18 In Inducing Oxaliplatin Resistance In Colorectal Cancer

Research Objective:Colorectal cancer is one of the most common malignant tumors in the gastrointestinal system,with high morbidity and mortality.Chemoresistance is a key factor affecting the prognosis of colorectal cancer patients.The molecular mechanism underlying the development of chemoresi stance in colorectal cancer cells is a current research hotspot,but the post-transcriptional regulatory mechanism remains unclear.The DHHC family has been shown to be closely related to chemoresistance.In this study,we aimed to investigate the role of ZDHHC18 in oxaliplatin resistance and explore the possibility of improving oxaliplatin efficacy by downregulating ZDHHC18 expression or inhibiting its palmitoyl transferase activity,and further explore the correlation between ZDHHC18 and FOXO signaling pathway.Research Methods:1.ZDHHC 18 expression was higher in colorectal cancer tissues than in normal tissues,and its expression was higher in oxaliplatin resistant group than in sensitive group.2.ZDHHC18 plays an important role in the sensitivity of colorectal cancer cells to oxaliplatin,and downregulation of ZDHHC18 expression significantly enhance the cytotoxic effect of oxaliplatin on tumor cells and inhibit tumor growth and proliferation.3.Downregulation of ZDHHC 18 expression can reduce the expression of FOXO 1 protein.Research Results:1.The expression of ZDHHC18 in colorectal cancer tissue was higher than that in normal tissue,and its expression was higher in resistant patients than in other oxaliplatin-sensitive patients,and the difference was statistically significant.2.ZDHHC 18 plays a crucial role in the sensitivity of colorectal cancer cells to oxaliplatin.Downregulation of ZDHHC18 expression significantly enhances the cytotoxicity of oxaliplatin against tumor cells and partially inhibits tumor growth and proliferation.3.Knockdown of ZDHHC18 expression can reduce the expression of FOXO1 protein.Research Conclusion:1.ZDHHC18 expression is positively correlated with chemoresistance in colorectal cancer.2.Downregulation of ZDHHC18 expression can be used as an intervention to improve oxaliplatin sensitivity in colorectal cancer.3.There is a certain correlation between ZDHHC18 expression and the FOXO signaling pathway.