The Malaysian journal of pathology · 2024
Oncolytic measles virus-induced cell killing in radio-resistant and drug-resistant nasopharyngeal carcinoma.
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Looi H K, Ngeow Y F, Kiew L V, Chang L Y, Ong H T
Аннотация
INTRODUCTION: The current first-line therapy for nasopharyngeal carcinoma (NPC) is often associated with long-term complications. Oncolytic measles virus (MV) therapy offers a promising alternative to cancer therapy. This study aims to investigate the efficacy of MV in killing NPC cells in vitro, both with or without resistance to radiation and drug therapy.
MATERIALS AND METHODS: NPC cell lines, CNE-1, CNE-2, HONE-1 and C666-1, were exposed to repeated cycles of gamma-irradiation and cisplatin to establish radio- and chemo-resistant cell lines, respectively. The expression of MV receptors, CD46 and nectin-4, were assessed with flow cytometer. To test the efficacy of viral infection, parental and both resistant NPC cells were infected with Measles-GFP-NIS in vitro. The progress of syncytia spread on NPC cells was monitored with fluorescence microscopy up to 60-hours post-infection (p.i.). MV-mediated killing was assessed using tetrazolium-based cell viability assay.
RESULTS: We established cisplatin-resistant (CR) NPC cell lines that exhibit more than two-fold shift in IC50 against cisplatin. Only CNE-2 and C666-1 acquired resistant traits after a cumulative 60-Gy gamma irradiation. All untreated parental and resistant NPCs expressed CD46 but not nectin-4 on their cell surface and were susceptible to MV infection. Syncytia were observable as early as 24 hours p.i. and cell loss was observable at 48-hours p.i. onwards. Interestingly, Measles-GFP-NIS shows higher infectivity in NPC with resistance phenotypes, except in CR-C666-1, and were killed more compared to their non-resistant counterparts.
CONCLUSION: Measles-GFP-NIS demonstrated potential as an alternative treatment in relapse, recurrent, or advanced stage NPC which often exhibits resistance towards chemo- and radiotherapy.
MATERIALS AND METHODS: NPC cell lines, CNE-1, CNE-2, HONE-1 and C666-1, were exposed to repeated cycles of gamma-irradiation and cisplatin to establish radio- and chemo-resistant cell lines, respectively. The expression of MV receptors, CD46 and nectin-4, were assessed with flow cytometer. To test the efficacy of viral infection, parental and both resistant NPC cells were infected with Measles-GFP-NIS in vitro. The progress of syncytia spread on NPC cells was monitored with fluorescence microscopy up to 60-hours post-infection (p.i.). MV-mediated killing was assessed using tetrazolium-based cell viability assay.
RESULTS: We established cisplatin-resistant (CR) NPC cell lines that exhibit more than two-fold shift in IC50 against cisplatin. Only CNE-2 and C666-1 acquired resistant traits after a cumulative 60-Gy gamma irradiation. All untreated parental and resistant NPCs expressed CD46 but not nectin-4 on their cell surface and were susceptible to MV infection. Syncytia were observable as early as 24 hours p.i. and cell loss was observable at 48-hours p.i. onwards. Interestingly, Measles-GFP-NIS shows higher infectivity in NPC with resistance phenotypes, except in CR-C666-1, and were killed more compared to their non-resistant counterparts.
CONCLUSION: Measles-GFP-NIS demonstrated potential as an alternative treatment in relapse, recurrent, or advanced stage NPC which often exhibits resistance towards chemo- and radiotherapy.