Abstract
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.
Highlights
Nasopharyngeal carcinoma (NPC) has a high occurrence rate in endemic areas of Southern China, Southeast Asia and North Africa and comprises a substantial health burden [1,2,3]
Most cases in endemic areas consist of WHO Type III anaplastic NPC with a high correlation of Epstein Barr virus (EBV) positivity while the majority of cases in non-endemic areas consist of keratinizing squamous cell carcinomas [5,6,7,8,9]
Co-treatment with GCV and arsenic trioxide (ATO) reduces tumor volume in vivo We have previously reported the ability of ATO treatment to induce ganciclovir susceptibility in EBV positive NPC cells in vitro [27]
Summary
Nasopharyngeal carcinoma (NPC) has a high occurrence rate in endemic areas of Southern China, Southeast Asia and North Africa and comprises a substantial health burden [1,2,3]. A majority of new cases occur in countries with limited resources for current therapies or early detection of NPC [4]. Most cases in endemic areas consist of WHO Type III anaplastic NPC with a high correlation of Epstein Barr virus (EBV) positivity while the majority of cases in non-endemic areas consist of keratinizing squamous cell carcinomas [5,6,7,8,9]. Current treatment for NPC consists of radiotherapy and chemotherapeutics with early detection associated The genetic and geographic pattern to NPC occurrence rates indicates multifocal etiology in that those of Cantonese descent born in North America display occurrence rates greater than their geographical counterparts, but less than that in endemic areas [10,11,12,13,14,15].
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