title: Selective cyclooxygenase-2 silencing mediated by engineered E. coli and RNA interference induces anti-tumour effects in human colon cancer cells.
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.
  
  
  CONCLUSIONS
  Our RNAi/InvColi-mediated approach offers a promising tool for a highly selective COX-2 blockade in vitro and in vivo.
authors: Department of Experimental Biology, University of Bologna, via Selmi 3, Bologna 40126, Italy. antonio.strillacci@unibo.it
authors: A
authors: A
authors: Strillacci
authors: C
authors: C
authors: Griffoni
authors: G
authors: G
authors: Lazzarini
authors: M C
authors: MC
authors: Valerii
authors: S
authors: S
authors: Di Molfetta
authors: F
authors: F
authors: Rizzello
authors: M
authors: M
authors: Campieri
authors: M P
authors: MP
authors: Moyer
authors: V
authors: V
authors: Tomasi
authors: E
authors: E
authors: Spisni
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000096:biosynthesis; D004926:Escherichia coli / Q000235:genetics*; D006801:Humans; D034622:RNA Interference; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051546:Cyclooxygenase 2; D015232:Dinoprostone