Effects Of BRD4 Inhibitors On Proliferation, Invasion And Apoptosis Of Hepatocyte Carcinoma Cells Huh7

Objective:Primary hepatic carcinoma(PHC)is one of the most common maligant tumors in China.New cases each year about 600,000 people around the world,an average of about 250,000 people die each year from liver cancer,and accounts for about 45% of them in China,the incidence of malignant tumors in the fifth,the mortality of cancer death in the third.The prevalence of the disease in middle-aged men was 5 to 1.90% of them are hepatocellular carcinama(HCC),and HCC has become one of the maliganant tumors that seriously threaten the life and health of our people.The canceration of liver cancer is caused by the loss of the tumor suppressor gene,the activation of oncogene,chromosome aberration,growth factor and abnormal receptor.Studies confirm that metastasis and recurrence are responsible for high mortality.Therefore,it is of great significance to study the metastasis and recurrence of hepatocellar carinoma to find the target of drug therapy,improve the curative effect,improve the progosis,and improve the survival rate.Bromodomain-containing protein 4(BRD4)is a family member of the bromine structure domain and the superterminal structure,which is combined with acetylated histone in the whole cell cycle.BRD4 regulates target gene expression by recruiting different transcriptional rugulatory factors.It plays an important role in rugulating cell gene transcription,cell cycle and inflammation.At present,several studies have found that the expression level of BRD4 is related to the development of multiple tumors,such as melanoma,acute myeloid leukemia,colon cancer and breast cancer.The inhibitor of targeted BRD4 protein can induce apoptosis of various tumors and inhibit proliferation,suggesting inhibition of BRD4 activity as a viable anti-tumor strategy.Currently,the role of BRD4 inhibitors in primary liver cancer is rarely reported,and more research is needed to explore its detailed functions.In this study,BRD4 inhibitors were used to treat hepotocellular carcinama cells,and their effects on proliferation,apoptosis and invasion of hepatocellular carcinoma were observed.Methods:The BRD4 activity of HCC cell line Huh7 cells was inhibited with BRD4 inhibitor GSK525762A.The effect of GSK525762 A on cell proliferation was detected by CCK-8 method after treatment of Huh7 cells 48 and 72h;Transwell method was used to detect the invasion ability of Huh7 cells after 48 and 72 h of different concentrations ofGSK525762A;The cell apoptosis of Huh7 cells after 48 and 72 h was detected by the method of flow cytometry and FITC staining.Results:GSK525762A had inhibitory effect on the proliferation of Huh7 cells,and the proliferation inhibition rate showed a time and concentration dependence,and the difference was statistically significant(p ? 0.05);After treatment of GSK525762 A,the number of perforated cells was less than 0 nmol/L,and showed a time dependence,and the difference was statistically significant(p?0.05);The early,late and total apoptosis rates of GSK525762 A were highter than 0 nmol/L,and the apoptosis rate increased with time,and the difference was statistically significant(p?0.05).Conclusion:Our study found that the BRD4 inhibitor GSK525762 A could inhibit the proliferation of Huh7 cells in hepatocellular carcinoma cells,reduce its invasion ability and promote the apoptosis of Huh7 cells.