The antitumor activity of TRAIL and IL-24 with replicating oncolytic adenovirus in colorectal cancer

L. Zhao, A. Dong, J. Gu, Z. Liu, Y. Zhang, W. Zhang, Y. Wang, L. He, C. Qian, Q. Qian, X. Liu

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Melanoma differentiation associated gene-7 (Mda-7)/IL-24 was previously cloned into ZD55 (an adenovirus with E1B55 deleted) to form ZD55-IL-24, which had much better antitumor effect than Ad-IL-24. According to its good antitumor properties, ZD55-IL-24 has been used in preclinical studies. But ZD55-IL-24 alone still could not completely eradicate established tumors in all nude mice. It was reported that IL-24 could induce and enhance the activity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (a member of tumor necrosis factor (TNF) superfamily). Accordingly, the combined use of ZD55-IL-24 and ZD55-TRAIL was carried out in this study. Treatment with both ZD55-IL-24 and ZD55-TRAIL could induce more significant apoptosis in cancer cells in vitro compared with ZD55-IL-24 or ZD55-TRAIL alone. The combination of the two replicative adenoviruses had better antitumor activity in vivo than that of single oncolytic adenovirus and led to complete eradication of xenograft tumors in all treated mice. Upregulation of TRAIL was observed in tumor cells infected with ZD55-IL-24 and studies of the apoptotic cascade regulators indicate that ZD55-IL-24 could further enhance the activation of apoptosis through the TNF family of death receptors. We demonstrated for the first time the potential therapeutic effect of combined ZD55-IL-24 with ZD55-TRAIL for the targeted therapy of cancer.

Original languageEnglish (US)
Pages (from-to)1011-1022
Number of pages12
JournalCancer Gene Therapy
Volume13
Issue number11
DOIs
StatePublished - Nov 7 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Cancer gene-virotherapy
  • Mda-7/IL-24
  • Oncolytic adenovirus
  • TRAIL
  • ZD55

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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