Recombinant oncolytic Newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cells
Abstract Background Anaplastic thyroid cancer (ATC) is one of the most aggressive of all solid tumors for which no effective therapies are currently available. Oncolytic Newcastle disease virus (NDV) has shown the potential to induce oncolytic cell death in a variety of cancer cells of diverse origi...
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| Format: | Article |
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BMC
2018-07-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4522-3 |
| _version_ | 1811198106096631808 |
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| author | Ke Jiang Cuiping Song Lingkai Kong Lulu Hu Guibin Lin Tian Ye Gang Yao Yupeng Wang Haibo Chen Wei Cheng Martin P. Barr Quentin Liu Guirong Zhang Chan Ding Songshu Meng |
| author_facet | Ke Jiang Cuiping Song Lingkai Kong Lulu Hu Guibin Lin Tian Ye Gang Yao Yupeng Wang Haibo Chen Wei Cheng Martin P. Barr Quentin Liu Guirong Zhang Chan Ding Songshu Meng |
| author_sort | Ke Jiang |
| collection | DOAJ |
| description | Abstract Background Anaplastic thyroid cancer (ATC) is one of the most aggressive of all solid tumors for which no effective therapies are currently available. Oncolytic Newcastle disease virus (NDV) has shown the potential to induce oncolytic cell death in a variety of cancer cells of diverse origins. However, whether oncolytic NDV displays antitumor effects in ATC remains to be investigated. We have previously shown that the oncolytic NDV strain FMW (NDV/FMW) induces oncolytic cell death in several cancer types. In the present study, we investigated the oncolytic effects of NDV/FMW in ATC. Methods In this study, a recombinant NDV expressing green fluorescent protein (GFP) was generated using an NDV reverse genetics system. The resulting virus was named after rFMW/GFP and the GFP expression in infected cells was demonstrated by direct fluorescence and immunoblotting. Viral replication was evaluated by end-point dilution assay in DF-1 cell lines. Oncolytic effects were examined by biochemical and morphological experiments in cultural ATC cells and in mouse models. Results rFMW/GFP replicated robustly in ATC cells as did its parent virus (NDV/FMW) while the expression of GFP protein was detected in lungs and spleen of mice intravenously injected with rFMW/GFP. We further showed that rFMW/GFP infection substantially increased early and late apoptosis in the ATC cell lines, THJ-16 T and THJ-29 T and increased caspase-3 processing and Poly (ADP-ribose) polymerase (PARP) cleavage in ATC cells as assessed by immunoblotting. In addition, rFMW/GFP induced lyses of spheroids derived from ATC cells in three-dimensional (3D) cultures. We further demonstrated that rFMW/GFP infection resulted in the activation of p38 MAPK signaling, but not Erk1/2 or JNK, in THJ-16 T and THJ-29 T cells. Notably, inhibition of p38 MAPK activity by SB203580 decreased rFMW/GFP-induced cleavage of caspase-3 and PARP in THJ-16 T and THJ-29 T cells. Finally, both rFMW/GFP and its parent virus inhibited tumor growth in mice bearing THJ-16 T derived tumors. Conclusion Taken together, these data indicate that both the recombinant reporter virus rFMW/GFP and its parent virus NDV/FMW, display oncolytic activities in ATC cells in vitro and in vivo and suggest that oncolytic NDV may have potential as a novel therapeutic strategy for ATC. |
| first_indexed | 2024-04-12T01:25:17Z |
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| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T01:25:17Z |
| publishDate | 2018-07-01 |
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| spelling | doaj.art-4f253ead1fe544ea860254a8f4f7662e2022-12-22T03:53:40ZengBMCBMC Cancer1471-24072018-07-0118111010.1186/s12885-018-4522-3Recombinant oncolytic Newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cellsKe Jiang0Cuiping Song1Lingkai Kong2Lulu Hu3Guibin Lin4Tian Ye5Gang Yao6Yupeng Wang7Haibo Chen8Wei Cheng9Martin P. Barr10Quentin Liu11Guirong Zhang12Chan Ding13Songshu Meng14Institute of Cancer Stem Cell, Dalian Medical University Cancer CenterDepartment of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural SciencesInstitute of Cancer Stem Cell, Dalian Medical University Cancer CenterInstitute of Cancer Stem Cell, Dalian Medical University Cancer CenterLaboratory Center, The Third People’s Hospital of Huizhou, Affiliated Hospital Guangzhou Medical UniversityInstitute of Cancer Stem Cell, Dalian Medical University Cancer CenterInstitute of Cancer Stem Cell, Dalian Medical University Cancer CenterDepartment of Dermatology of First Affiliated Hospital, Dalian Medical UniversityInstitute of Cancer Stem Cell, Dalian Medical University Cancer CenterInstitute of Cancer Stem Cell, Dalian Medical University Cancer CenterThoracic Oncology Research Group, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences St. James’s Hospital and Trinity College DublinInstitute of Cancer Stem Cell, Dalian Medical University Cancer CenterCentral laboratory, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical UniversityDepartment of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural SciencesInstitute of Cancer Stem Cell, Dalian Medical University Cancer CenterAbstract Background Anaplastic thyroid cancer (ATC) is one of the most aggressive of all solid tumors for which no effective therapies are currently available. Oncolytic Newcastle disease virus (NDV) has shown the potential to induce oncolytic cell death in a variety of cancer cells of diverse origins. However, whether oncolytic NDV displays antitumor effects in ATC remains to be investigated. We have previously shown that the oncolytic NDV strain FMW (NDV/FMW) induces oncolytic cell death in several cancer types. In the present study, we investigated the oncolytic effects of NDV/FMW in ATC. Methods In this study, a recombinant NDV expressing green fluorescent protein (GFP) was generated using an NDV reverse genetics system. The resulting virus was named after rFMW/GFP and the GFP expression in infected cells was demonstrated by direct fluorescence and immunoblotting. Viral replication was evaluated by end-point dilution assay in DF-1 cell lines. Oncolytic effects were examined by biochemical and morphological experiments in cultural ATC cells and in mouse models. Results rFMW/GFP replicated robustly in ATC cells as did its parent virus (NDV/FMW) while the expression of GFP protein was detected in lungs and spleen of mice intravenously injected with rFMW/GFP. We further showed that rFMW/GFP infection substantially increased early and late apoptosis in the ATC cell lines, THJ-16 T and THJ-29 T and increased caspase-3 processing and Poly (ADP-ribose) polymerase (PARP) cleavage in ATC cells as assessed by immunoblotting. In addition, rFMW/GFP induced lyses of spheroids derived from ATC cells in three-dimensional (3D) cultures. We further demonstrated that rFMW/GFP infection resulted in the activation of p38 MAPK signaling, but not Erk1/2 or JNK, in THJ-16 T and THJ-29 T cells. Notably, inhibition of p38 MAPK activity by SB203580 decreased rFMW/GFP-induced cleavage of caspase-3 and PARP in THJ-16 T and THJ-29 T cells. Finally, both rFMW/GFP and its parent virus inhibited tumor growth in mice bearing THJ-16 T derived tumors. Conclusion Taken together, these data indicate that both the recombinant reporter virus rFMW/GFP and its parent virus NDV/FMW, display oncolytic activities in ATC cells in vitro and in vivo and suggest that oncolytic NDV may have potential as a novel therapeutic strategy for ATC.http://link.springer.com/article/10.1186/s12885-018-4522-3Anaplastic thyroid cancer (ATC)Newcastle disease virus (NDV)p38 MAPKGreen fluorescent protein (GFP)Apoptosis |
| spellingShingle | Ke Jiang Cuiping Song Lingkai Kong Lulu Hu Guibin Lin Tian Ye Gang Yao Yupeng Wang Haibo Chen Wei Cheng Martin P. Barr Quentin Liu Guirong Zhang Chan Ding Songshu Meng Recombinant oncolytic Newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cells BMC Cancer Anaplastic thyroid cancer (ATC) Newcastle disease virus (NDV) p38 MAPK Green fluorescent protein (GFP) Apoptosis |
| title | Recombinant oncolytic Newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cells |
| title_full | Recombinant oncolytic Newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cells |
| title_fullStr | Recombinant oncolytic Newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cells |
| title_full_unstemmed | Recombinant oncolytic Newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cells |
| title_short | Recombinant oncolytic Newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cells |
| title_sort | recombinant oncolytic newcastle disease virus displays antitumor activities in anaplastic thyroid cancer cells |
| topic | Anaplastic thyroid cancer (ATC) Newcastle disease virus (NDV) p38 MAPK Green fluorescent protein (GFP) Apoptosis |
| url | http://link.springer.com/article/10.1186/s12885-018-4522-3 |
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