Inhibition of nasopharyngeal carcinoma growth by RTA-expressing baculovirus vectors containing oriP

Leyao Wang, Liang Shan, Kwok Wai Lo, Juan Yin, Yuanyuan Zhang, Ren Sun, Jiang Zhong

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Nasopharyngeal carcinoma (NPC) is closely associated with latent Epstein-Barr virus (EBV) infection. Activation of latent EBV into lytic replication by introducing viral lytic gene BRLF1 (RTA) has been shown to be a potential approach to suppress the growth of EBV-associated NPC tumor. Methods: The baculovirus vectors with RTA expression cassette (BV-R), RTA and the EBV latent replication origin (OriP, BV-RO), or RTA, OriP and EBNA-1 gene (BV-ROE-CMV), were constructed and examined for their ability to mediate RTA expression, initiate lytic replication and induce cell death in EBV-positive cell lines Hone1-EBV, HK1-EBV and C666-1 in vitro. Their effect to inhibit the growth of EBV-positive NPC tumors was also evaluated in nude mice. Results: The baculovirus vectors BV-RO and BV-ROE-CMV mediated efficient expression of RTA in EBV-positive NPC cells. Lytic EBV replication and cell death were observed in these infected cells. Both vectors also significantly inhibited the growth of EBV-positive NPC tumor in nude mice. EBV early lytic gene expression and tumor cell death were observed in these treated tumors. Conclusions: The presence of OriP improved the performance of the RTA-expressing baculovirus vectors to induce EBV lytic replication and cell death in vitro, and suppress the growth of EBV positive NPC tumors in vivo. By confining RTA and EBNA-1 expression to EBV-positive cells, BV-RO is expected to be a better candidate in application than BV-ROE-CMV in the long term.

Original languageEnglish
Pages (from-to)1124-1133
Number of pages10
JournalJournal of Gene Medicine
Volume10
Issue number10
DOIs
StatePublished - Dec 1 2008

Keywords

  • Baculovirus vector
  • Epstein-Barr virus
  • Gene therapy
  • Nasopharyngeal carcinoma
  • OriP/EBNA-1
  • RTA

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