The Effect Of Naringin On Potassium Current In Hepatoma Cell Line SMMC-7721 And Its Anticancer Effect

Background:Ion channels are membrane proteins that transport ions across membranes and play an important role in cell proliferation,migration and invasion.Studies have shown that the expression and activity of ion channels are abnormal during the development and growth of cancer cells.When ions move in and out of ion channels,they generate ion channel currents.With the development of patch clamp technology,ion channel current on cancer cell membrane has become a new research hotspot.Potassium channel is the largest type of ion channel family.Studies have shown that there is abnormal potassium channel current in hepatocellular carcinoma cells,which may be related to abnormal proliferation,migration and invasion of hepatocellular carcinoma cells.Ba CI₂is a recognized potassium channel inhibitor,which can effectively inhibit potassium channel currents.Naringin is a kind of dihydroflavonoid glycoside in citrus fruits.It is a kind of traditional Chinese medicine monomer,which has anti-inflammatory,antioxidant and anticancer effects.It is a new antitumor drug.Studies have shown that naringin can inhibit the proliferation,migration and invasion of hepatocellular carcinoma cells by influencing the expression of cell cycle related proteins and the activities of various enzymes during signal transduction.However,the effect of naringin on potassium channel current in hepatocellular carcinoma cells has not been reported.Objective:In this study,the effects of naringin on potassium channel current of SMMC-7721 cells were investigated,and combined with its effects on the proliferation,migration and invasion of SMMC-7721 cells,potassium channel current was proposed as a new therapeutic target for liver cancer,providing a new direction for liver cancer treatment.Methods:Cultured hepatocellular carcinoma SMMC-7721 cells were digested with pancreatic enzymes for a period of time,then the single cell suspension was made by blowing.Ion channel currents were recorded in the whole cell membrane mode,and Ba CI₂,a potassium ion current inhibitor,was used to validate the currents.The effects of naringin at different concentrations and the combination of naringin and Ba CI₂on the changes of potassium channel currents were detected.The effects of naringin,Ba CI₂and the combination of naringin and BACI₂on the migration,proliferation and invasion of hepatocellular carcinoma cells were detected by wound healing test,CCK-8 test and Transwell test,respectively.Results:（1）Naringin could significantly inhibit the potassium channel current of SMMC-7721 cells,and the effect became more obvious with the increase of concentration（1,5,10,20 and 40μM）.The inhibition rates were 12.51±3.59%,18.44±3.14%,46.13±4.33%,80.35±1.24%and 96.12±0.86%,respectively,and the IC₅₀value was 12.28±0.45μM.（2）Naringin can inhibit the proliferation,migration and invasion of SMMC-7721 cells in a concentration-dependent manner.（3）Ba CI₂can inhibit potassium channel currents of SMMC-7721 cells in a concentration-dependent manner（100,200,400,600,800,1000 and 1200μM）;（4）Ba CI₂inhibited the proliferation,migration and invasion of SMMC-7721 cells in a concentration-dependent manner（100,400,800 and 1200μM）.（5）Combined administration（20μM naringin+1200μM Ba CI₂）had better inhibitory effects than single administration in both current and cell proliferation,migration and invasion experiments.Conclusion:Naringin can inhibit the proliferation,migration and invasion of SMMC-7721 cells in a concentration-dependent manner.Inhibition of potassium channel current may be one of the reasons why naringin inhibits proliferation,migration and invasion of SMMC-7721 cells.