| Background:Anaplastic thyroid cancer(ATC)is one of the high mortality endocrine malignancies.Because of its unstable genetic characteristics and complex genetic alterations,there has been no effective treatment.Conventional methods such as surgical resection and radiotherapy are not ideal.At present,a series of new treatments,such as gene therapy,induced differentiation therapy and protein inhibitor therapy,are far from mature.Gene therapy is still in its infancy.The treatment of induced differentiation has not yet undergone large-scale clinical trials,and the effect of treatment is yet to be verified.However,the treatment of protein inhibitors has the disadvantages of low oral utilization,low specificity and large side effects.It also needs further study.It has been reported that,oncolytic Newcastle disease virus(NDV)can infect and induce cell death in various tumors,but has no cytotoxicity on normal cells.So the oncolytic virus as a novel treatment method has the broad application prospect.However,whether Newcastle disease virus infection ATC cells has not been reported.In the present study,we investigated the oncolytic effects of r FMW/GFP in ATC.Methods:In this study,r FMW/GFP was examined in two main approaches in vivo,in mice,using the ATC cells.Initially,the cells were infected with r FMW/GFP and the mechanism of antitumor activities determined by biochemical and morphological experiments.Nude mice were also treated with r FMW/GFP for in vivo studyResults:(1)We generated a recombinant NDV expressing green fluorescent protein(r FMW/GFP).(2)r FMW/GFP,replicated robustly in ATC cells as did its parent virus(NDV/FMW),and there was no significant difference in the ability of the virus replicate.(3)In 2D culture conditions,r FMW/GFP infection substantially increased early and late apoptosis in the ATC cell lines,THJ-16 T and THJ-29 T and increased caspase-3processing and Poly(ADP-ribose)polymerase(PARP)cleavage in ATC cells as assessed by immunoblotting.In three-dimensional(3D)cultures,r FMW/GFP inhibits the ability of ATC cells’ sphere formation.(4)We further demonstrated that r FMW/GFP infection resulted in the activation of p38 MAPK signaling in THJ-16 T and THJ-29 T cells.Notably,inhibition of p38 MAPK activity by SB203580 decreased r FMW/GFP-induced cleavage of caspase-3 and PARP in ATC cells.(5)Both r FMW/GFP and its parent virus(NDV/FMW)inhibited tumor growth in mice bearing THJ-16 T derived tumors.Conclusion:In the present study,we demonstrated that recombinant reporter virus r FMW/GFP displays oncolytic activities in ATC cells via p38 MAPK signaling pathway and represents a novel potential therapeutic strategy for ATC. |
