Co-treatment with arsenic trioxide and ganciclovir reduces tumor volume in a murine xenograft model of nasopharyngeal carcinoma

We have previously shown that disruption of promyelocytic leukemia nuclear bodies (PML NBs) is sufficient to activate the EBV lytic cycle thus making infected cells susceptible to ganciclovir (GCV) mediated killing in vitro. Here we show that co-administration of GCV and arsenic trioxide (ATO), a PM...

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Bibliographic Details
Published in:Virology journal 2013-05, Vol.10 (1), p.152-152, Article 152
Main Authors: Sides, Mark D, Sosulski, Meredith L, Luo, Fayong, Lin, Zhen, Flemington, Erik K, Lasky, Joseph A
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antiviral Agents - administration & dosage
apoptosis
arsenic
Arsenic Trioxide
Arsenicals - administration & dosage
Carcinoma
Complications and side effects
Disease Models, Animal
Dosage and administration
Drug therapy
Drug Therapy, Combination - methods
Epstein-Barr virus
Ganciclovir
Ganciclovir - administration & dosage
Genetic aspects
Heterografts - drug effects
Humans
Leukemia
Mice
Nasopharyngeal cancer
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms - drug therapy
Oxides - administration & dosage
patients
Physiological aspects
Proteins
Risk factors
Treatment Outcome
Tumor Burden - drug effects
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Summary:We have previously shown that disruption of promyelocytic leukemia nuclear bodies (PML NBs) is sufficient to activate the EBV lytic cycle thus making infected cells susceptible to ganciclovir (GCV) mediated killing in vitro. Here we show that co-administration of GCV and arsenic trioxide (ATO), a PML NB disruptor, reduces tumor volume in a xenograft model of nasopharyngeal carcinoma utilizing CNE1 cells. When administered at pharmacologic levels, both GCV and ATO reduced tumor growth while co-treatment with GCV + ATO resulted in a diminution of tumor volume. Treatment with GCV or ATO individually resulted in an increased number of apoptotic cells while co-treatment with GCV + ATO synergistically induced apoptosis. Treatment with ATO or co-treatment with GCV + ATO resulted in expression of EBV lytic proteins. These data suggest that co-treatment with GCV + ATO may provide an effective treatment for nasopharyngeal carcinoma patients.
ISSN:1743-422X
1743-422X
DOI:10.1186/1743-422X-10-152