Selective cyclooxygenase-2 silencing mediated by engineered E. coli and RNA interference induces anti-tumour effects in human colon cancer cells

A. Strillacci, C. Griffoni, G. Lazzarini, M. C. Valerii, S. Di Molfetta, F. Rizzello, M. Campieri, M. P. Moyer, V. Tomasi, E. Spisni

Research output: Contribution to journalArticle

Abstract

Background:Cyclooxygenase-2 (COX-2) overexpression is strongly associated with colorectal tumourigenesis. It has been demonstrated that the chronic use of non-steroidal anti-inflammatory drugs (COX inhibitors) partially protects patients from colorectal cancer (CRC) development and progression but induces severe cardiovascular side effects. New strategies for selective COX-2 blockade are required.Methods:We developed an improved technique, based on RNA interference (RNAi), to gain a selective COX-2 silencing in CRC cells by a tumour-dependent expression of anti-COX-2 short-hairpin RNA (shCOX-2). Anti-COX-2 shRNA-expressing vectors were delivered in CRC cells (in vitro) and in colon tissues (ex vivo) using engineered Escherichia coli strains, capable of invading tumour cells (InvColi).Results:A highly tumour-dependent shCOX-2 expression and a significant COX-2 silencing were observed in CRC cells following InvColi strain infection. Cyclooxygenase-2 silencing was associated with a strong reduction in both proliferative and invasive behaviour of tumour cells. We also demonstrated a pivotal role of COX-2 overexpression for the survival of CRC cells after bacterial infection. Moreover, COX-2 silencing was achieved ex vivo by infecting colon tissue samples with InvColi strains, leading to anti-inflammatory and anti-tumour effects.Conclusion:Our RNAi/InvColi-mediated approach offers a promising tool for a highly selective COX-2 blockade in vitro and in vivo.

Original languageEnglish
Pages (from-to)975-986
Number of pages12
JournalBritish Journal of Cancer
Volume103
Issue number7
DOIs
Publication statusPublished - Sep 28 2010

Keywords

  • COX-2
  • CRC
  • E. coli
  • RNAi

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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    Strillacci, A., Griffoni, C., Lazzarini, G., Valerii, M. C., Di Molfetta, S., Rizzello, F., Campieri, M., Moyer, M. P., Tomasi, V., & Spisni, E. (2010). Selective cyclooxygenase-2 silencing mediated by engineered E. coli and RNA interference induces anti-tumour effects in human colon cancer cells. British Journal of Cancer, 103(7), 975-986. https://doi.org/10.1038/sj.bjc.6605859