Study On The Combined Therapy Of Baicalin And NsPEFs In The Treatment Of HCC

Background:Liver cancer has become a prevalent and lethal cancer worldwide.Nanosecond pulsed electric fields(ns PEFs)is emerged as a potential curative modality to ablate hepatocellular carcinoma(HCC),however,the application in HCC local ablation is usually limited by the insufficiency of patients' liver function.While baicalin,a flavonoid isolated from Scutellaria baicalensis Georgi,has been proven to possess both anti-tumor and protective effects.Our study aimed to estimate different responses of hepatic cancer cells and hepatocytes to the combination of ns PEFs and baicalin.Material and methods:1.We used cell counting kit-8(CCK-8)assay to examine cell viabilities of ns PEFs and baicalin treated HCC cells and normal hepatocytes,in order to demonstrate the effect on proliferation.2.Flow cytometry(FCM)and western-blot(WB)assays were also employed to determine the cell death pathways involved in the combinational treatment of ns PEFs and baicalin.3.Mitochondrial transmembrane potential(MTP)and reactive oxygen species(ROS)were checked as well through JC-1 and fluorescent probe to further investigate the mechanisms of the different death modes stimulated by combination treatment.Results:1.We discovered a difference in sensitivity between normal hepatocytes and HCC cells to the stimuli of ns PEFs while HCC cells were more sensitive.Meanwhile,baicalin was more toxic to HCC cells compared to normal hepatocytes,which was more obvious at 24 h than 48 h.2.The combined therapy exhibited a stronger therapeutic inhibition on cancer cells than sole utility of ns PEFs whereas a recovery occurred on normal hepatocytes by baicalin after ns PEFs treatment,which could be considered as a dual-function.3.Treatment of ns PEFs was able to trigger various cell death pathways,which were apoptosis and necrosis on normal hepatocytes and HCC cells,respectively.4.Low concentration of baicalin recovered the ns PEFs-induced mitochondrial transmembrane potential(MTP)dissipation and reactive oxygen species(ROS)generation in normal hepatocytes whereas showed relatively no effects in HCC cells.Conclusion:Our work provided an advantageous therapy for HCC through the enhanced combination treatment of ns PEFs and baicalin,with which could improve the tumor-ablation effect and alleviate the injury of hepatic tissues simultaneously.Mechanism experiments presented different cell death modes induced by ns PEFs,which could be the basis of such dual-function.