The Inhibition Effect Of Newcastle Disease Virus D90Strain On Human Gastric Cancer Cell BGC-823in Vivo And Invitro

Gastric carcinoma is one of the malignant tumors of human alimentary tract in developingcountry. It is also one of the common tumors with high mortality all over the world. For thepatients with tumor metastasis, there is a lower chance of survival after treated by surgery orchemotherapy. Recent reports indicate that the oncolytic virus therapy is a promising pattern.Many oncolytic viruses are found, including adenovirus, rabies virus, polio virus, herpes simplexvirus, influenza a virus, measles virus and Newcastle disease virus (NDV). NDV, a poultryparamyxovirus, is considered as an important oncolytic virus to selectively replicate andproliferate in tumor cells rather than in human normal cells. It is a safety reagent, besides slightflu-like symptoms and conjunctivitis. Several clinical trials show that NDV is an efficient andsafe reagent for the tumor treatment. Now there are some NDV strains, such as oncolytic virusMTH68/H, PV-701, and73-T, non-oncolytic strain Ulster, attenuated strain HUJ (OV001), usedas treatment for human cancer. NDV-D90strain, a new separation NDV strain, had beencharacterized by efficient and rapid oncolytic effect for cancer cells.In this study, for revealing the proliferation ability of NDV-D90in gastric cancer BGC-823cell, the virus titer was detected in infected BGC-823cells supernatant. Cytotoxicity ofNDV-D90to BGC-823cells was analyzed when the virus transfect BGC-823cells at differentMOI in order to demonstrate inhibitory action and lethality on gastric carcinoma cells. This studyshowed a positive effect of NDV-D90on BGC-823cell replication and proliferation as well asstrong cytotoxic or killing activity. The maximum virus titer reached up to1010TCID50/0.1mlat60h after infection and More than80%cancer cells dead. The higher MOI the higher mortalityrate and the faster death occurred. Flow cytometry indicated79%BGC-823cells apoptosis at72h after infection with MOI=1. Of note, the apoptosis rate was considerably increased with thehigher of MOI. Tumor cell infestation experiment showed that the aggressiveness of BGC-823cells was inhibited by NDV-D90. A BGC-823cell labeled with luciferase naming BGC-823-luciwas constructed by transforming GV260lentivirus vectors inserted luciferase gene to make themodel of transplantation tumor nude mice. The size of transplantation tumor injected withNDV-D90was getting smaller and smaller than that of PBS control. The results of in vivoimaging showed a lower fluorescent signal than control. The larger area of necrosis in the tumor tissue section with HE staining was observed in NDV-D90group but the control cancer cellsnormally grew up. Our data indicated that NDV-D90could inhibit the growth of BGC-823cellsand maybe an oncolytic agent for cancer cell.