Tachypleus Tridentatus Lectin Enhances Oncolytic Vaccinia Virus Replication To Suppress In Vivo Hepatocellular Carcinoma Growth

Hepatic carcinoma is a type of cancer with a high incidence.Investigation shows that the current mortality of hepatic carcinoma in China is second only to lung cancer and gastric cancer,which seriously threatens human health.Because of it has many predisposing factors can inducce hepatic carcinoma,and the development speed of hepatic carcinoma is fast,the prognosis is poor,and postoperative recurrence or metastasis is easily.Therefore,the research on the pathogenesis and treatment of hepatic carcinoma is a quantum challenge in current medical research.With the development of molecular biology and genetic engineering technology,targeted gene-virus combination therapy has become a research hotspot in the treatment of hepatic carcinoma.In this study,a recombinant gene oncolytic vaccinia virus carrying the marine agglutinin gene was constructed on the basis of targeted gene-virus combination therapy to study its therapeutic effect on the subcutaneous transplantation model of hepatocarcinoma MHCC97-H cells in nude mice.Tachypleus tridentatus LPS-binding protein is a LPS-binding protein in Tachypleus tridentatus that can block strong inflammatory responses produce by Lipopolysaccharides（LPS）.Oncolytic vaccinia viruses（oncoVV）have the capacity to induce specific lysis of tumor cells and indirectly impact tumor growth via vascular shutdown and virus replicate in tumor cells.onco VV can be replicated in tumor cells without being cleared mainly because it can evade some of the body’s immune responses.But therapeutic doses must be very high in order to evade antibodies and other components of the immune system.We combined the advantages of exogenous genes woth vaccinia virus vectors,to construct a novel oncolytic vaccinia virus oncoVV-TTL.To study the killing mechanism of this novel oncolytic vaccinia virus against hepatocellular carcinoma cells,we used low-dose oncoVV and oncoVV-TTL to treated hepatocellular carcinoma cells.PBS served as a control.We found that oncoVV-TTL has significantly higher replication capacity than oncoVV by TCID₅₀ test.In order to further verify the effects of oncoVV-TTL on hepatocellular carcinoma cells,we established a hepatocellular carcinoma mouse modle.The oncoVV-TTL showed significant antitumor activity.We further explored the mechanism of the virus through in vitro experiments.Our data demonstrated that oncoVV-TTL has signification downregulated the expression of antiviral proteins,such as MAVS,IFI16,and MDA5.We further showed that the replication of the virus is related to phosphorylation of the ERK.Therefore,we further cooperated with the virus by using the ERK inhibitor U0126.The experimental results showed that the replication of the control virus oncoVV was not affected cooperated with the inhibitor.However,the oncoVV-TTL replication was significantly suppressed by U0126.All the results together showed that TTL could increase the replication of the virus by relying on the ERK pathway.This novel recombinant virus has a better antitumor effect on hepatocellular carcinoma.In the follow-up study,low doses of virus might be used to treat patients with liver cancer,providing a novel treatment for cancer patients.