MnAs Nano-drug Inhibits Invasion And Metastasis Of Hepatocellular Carcinoma

Background and objectives:In the treatment of cancer,drugs can effectively inhibit the growth and metastasis of tumor and prolong the survival time of patients.At present,Liver cancer is not sensitive to chemotherapy and radiotherapy.Though surgical resection is still the first choice for clinical treatment of liver cancer,the development of new anti-cancer drugs can increase the therapeutic effect of liver cancer.Nano-drugs can better improve the target in the treatment of cancer.It gives a profound significance for the treatment of liver cancer.In this study,we investigated the inhibitory effect of the new nano-drug(MnAsOx@SiO2-ZW)on the metastasis of hepatocellular carcinoma,analysis of therapeutic effect and mechanism of nano-drugs.Experimental methods:We used CCK-8 cytotoxicity assay to test the half maximal inhibitory concentration(IC50)of different types of hepatocellular carcinoma cells.ICP-MS assay was used to detect intracellular arsenic ions concentration.The effects of nano-drugs on the migration and invasion of hepatocellular carcinoma cells were studied by Wound scratch assay and Transwell assay in vitro.To study the inhibitory effect of nano-drugs on the metastasis of liver cancer and its effect on the growth of tumor,through naked mouse tumor formation experiment and fluorescence imaging technology in vivo,By use separation of circulating tumor cells in the peripheral blood of mouse model of liver cancer on microfluidic technology method to research the treatment on circulating tumor cells where there will be changes.Results:CCK-8 cytotoxicity assay show that the nano-drugs have much higher cytotoxicity on SMMC-7721 and BEL-7402 hepatoma cells comparing with conventional ATO:the IC50 was 6.61uM,9.89uM,lower than the ATO(14.27uM,24.25uM).In the ICP-MS experiment,the intracellular arsenic content of nano-drug treated cells was significantly higher(39.13ng)than ATO(22.14ng).Which means Nano-drug can improve the intake of arsenic in hepatoma cells,and the significantly increasing intracellular concentration of arsenic could easily get tumor cells killed.Wound scratch assay and Transwell assay showed that the migration and invasion ability of tumor cells were decreased after the treatment with nano-drugs,there was significantly different from control group.The results of fluorescence imaging in vivo also showed that the growth and metastasis of HCC were significantly inhibited in mice model.At the same time,mechanism of the nano-drugs have also been further study,we detected the microfluidic chip and results showed that the mice model which was after nano-drug treatment in vivo,had dramatically fewer numbers of circulating tumor cells than other treatment,result in nano-drug can effectively eliminate circulating tumor cells in the blood,eventually reducing the metastatic ability of hepatocellular carcinoma in animal model.Conclusion:MnAsOx@SiO2-ZW has a stronger power than ATO for hepatoma cells.It can effectively eliminate circulating tumor cells to inhibit the growth and metastasis of hepatocellular carcinoma.