| Liver cancer's incidence rate is the sixth highest in malignant tumor over the world,and the number of global deaths per year is the fourth among malignant tumors.China is the country with the highest incidence of liver cancer,and more than 300,000 people die every year from liver cancer.At present,the treatment methods and drugs for liver cancer are very limited with problems such as poor prognosis and high recurrence rate.In recent years,oncolytic virus have developed very rapidly,showing good results in a variety of tumor treatments,and having great development prospects.Enterovirus is a small RNA virus that mainly causes Hand-foot-mouth Disease in children.Previous studies have shown that coxsackievirus group B type 3(CVB3)in enterovirus has great potential for the development of oncolytic virus for its good oncolytic activity against cervical cancer,endometrial cancer and lung cancer cells.This study has the following goals.Firstly,this study analyzes the oncolytic activity of CVB3 on a variety of different tumor cells more comprehensively.Secondly,this research initially reveal the oncolytic activity spectrum of CVB3.And thirdly,we focus on the feasibility of using CVB3 to develop new oncolytic viruses against liver cancer.Finally,we expect to develop new anti-tumor evaluation of liver cancer drugs.In this study,we first investigated the killing effect of CVB3 on 33 tumor cells belonging to 15 different cancer species in vitro,and systematically investigated the oncolytic effect and potential of CVB3.The results show that CVB3 has a good killing effect on tumor cells such as cervical cancer,endometrial cancer and lung cancer,and it also has tumor cells for various cancers such as liver cancer,colorectal cancer,breast cancer and pancreatic cancer.This study found that C VB3 has a high oncolytic activity on liver cancer cells.In vitro,CVB3 has strong killing ability for all 8 liver cancer cells used in this study,and it can significantly kill the above 8 liver cancers at a lower dose(MOI=0.01).In this study,we further evaluated the killing effect of CVB3 on hepatocarcinoma tumors in animals using a human hepatocarcinoma cell tumor model.The results showed that CVB3 significantly inhibited the growth of hepatocarcinoma HepG2 cell tumors in nude mice and caused necrosis of tumor cells.This study further explored the oncolytic mechanism of CVB3.The high expression of CVB3 virus receptor CAR protein in hepatocarcinoma cells may be an important cause of CVB3 susceptibility to liver cancer cells.C.VB3 infection can induce apoptosis of liver cancer cells and cause DAMPs to be released from infected cellsIn this study,the in vitro evaluation method was also used to filter potential liver cancer suppression or therapeutic drugs from an "Approved Drug Library".The purpose of this study is to apply the "old drug new use" strategy to screen possible listed drugs with liver cancer inhibition ability,and also provide a basis for future possible oncolytic virus combination drug research.This study evaluated the anti-hepatocarcinoma cell activity of 1818 small molecule drugs.The results showed that 30 of the drug molecules have certain anti-hepatocarcinoma cell activity,which can be further used as an anti-tumor drug candidate for follow-up research.Among them,Auranofin has relatively good anti-hepatocarcinoma cell activity,and the in vitro killing experiment of 8 liver cancer cell lines shows that the drug has the potential to develop anti-hepatocarcinoma drugsIn summary,this study more comprehensively reveals the oncolytic activity spectrum of CVB3 on human tumor cells,and found that CVB3 has a good Anti-hepatoma ability,and has a good potential for the development of new liver cancer treatment of oncolytic virus drugs.At the same time,this study also screened and obtained some small molecule drugs with Anti-hepatoma potential.This study can provide an important basis for further research on new drugs and methods for the treatment of liver cancer. |
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