Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro

Ordonez,Paula; Nandakumar,Athira; Koriyama,Chihaya; Yamomoto,Megumi; Akiba,Suminori

doi:10.3892/mmr.2016.5496

Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro

Authors:
- Paula Ordonez
- Athira Nandakumar
- Chihaya Koriyama
- Megumi Yamomoto
- Suminori Akiba
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Affiliations: Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan, Department of Basic Medical Sciences, National Institute for Minamata Disease, Minamata, Kumamoto 867‑0008, Japan
Published online on: July 11, 2016 https://doi.org/10.3892/mmr.2016.5496
Pages: 2359-2367

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Abstract

Epstein-Barr virus (EBV) infection in tumor cells is usually restricted to the latent form, indicating that the induction of viral lytic infection may present a novel approach for the treatment of EBV‑associated tumors. By contrast, EBV lytic replication is inhibited by high‑levels of nuclear factor (NF)‑κB, which suggests that NF‑κB inhibitors may activate lytic replication from the latent form. In the current study, the addition of NF‑κB inhibitors (Bay11‑7082, Z‑LLF‑CHO and aspirin) was observed to induce the EBV lytic genes BZLF1, BRLF1 and BMRF1 in EBV‑positive gastric cancer (GC) cells. Both EBV‑positive and ‑negative GC cells were treated with different concentrations of anti‑herpes agents and the cytotoxic effects were measured at different time points following induction of EBV lytic replication. A marginal dose‑ and time‑dependent reduction in cell viability was observed for EBV‑positive and‑negative GC cells. The cytotoxic effects of NF‑κB inhibitors on EBV‑positive GC cells were enhanced by the addition of the anti‑herpes agents, ganciclovir, acyclovir, foscarnet and brivudine (P<0.05). However, there was no significant synergistic effect on EBV‑negative GC cells. The combination of 5 mM aspirin and ganciclovir exhibited the highest cytotoxic effect in EBV‑positive GC cells (CC50=7.2 µg/ml).

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