Molecular Mechanisms Of CMPD-1 Induced G2/M Arrest And Apoptosis In Gastric Cancer MKN-45 Cells

Gastric cancer is a malignant tumor derived from the epithelium of the gastric mucosa,occuping the fourth highest morbidity rate of cancers worldwide.Although the incidence rate has declined,it has become younger in recent years.The characteristics of gastric cancer in our country showed low early diagnosis rate,low surgical removal rate and poor prognosis.There is no standard and effective treatment for advanced gastric cancer,so higher therapeutic efficiency and low toxic drugs is urgently needed.In this study,CMPD-1 used as a wildly MK2 Protein kinase inhibitor was employed to find its impact on gastric cancer cell proliferation,apoptosis and cell cycle using colony formation assay and flow cytometry analysis.Along with its anti-proliferation effect on gastric cancer cell line MKN-45 and SGC7901,CMPD-1 also induced massive apoptosis and significant G2/M phase arrest in a time-dependent and dose-dependent manner in MKN-45 cells respectively.Furthermore,Western blot confirmed that the expression of anti-apoptotic proteins Bcl-2 was decreased while BAX,Cytochrome c release and cleaved PARP were increased.In addition,oncogene c-Myc was down-regulated in response to CMPD-1 treatment.Our results demonstrated that CMPD-1 has anti-tumor effect on human gastric cancer cell line MKN-45 possibly via down-regulating oncogene c-Myc expression.It may be become a potential lead compound for the treatment of gastric cancer.