title: RNAi-based strategies for cyclooxygenase-2 inhibition in cancer.
abstract: Cyclooxygenase-2 (COX-2) enzyme has been involved in the tumorigenesis and in the progression of colorectal cancer (CRC). The use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors has been proposed for the prevention and the treatment of this relevant neoplastic disease. In the light of an innovative alternative to these pharmacological approaches, we review here the possible strategies to achieve a strong and selective inhibition of COX-2 enzyme by using the mechanism of RNA Interference (RNAi) targeted against its mRNA. Anti-COX-2 siRNA molecules (siCOX-2) can be generated in CRC cells from short hairpin RNA (shRNA) precursors, delivered in vitro by a retroviral expression system, and induce a significant and stable silencing of overexpressed COX-2 in human colon cancer cells. As a safer alternative to viral approach, nonpathogenic bacteria (E. coli) can be engineered to invade eukaryotic cells and to generate siCOX-2 molecules in cancer cells. Moreover, the involvement of miRNAs in COX-2 posttranscriptional regulation opens up the possibility to exploit an endogenous silencing mechanism to knockdown overexpressed COX-2. Thus, these recent strategies disclose new challenging perspectives for the development of clinically compatible siRNA or miRNA capable of selectively inhibiting COX-2 enzyme.
authors.affiliation: Department of Experimental Biology, University of Bologna, Via Selmi 3, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Strillacci
authors.forename: Cristiana
authors.initials: C
authors.lastname: Griffoni
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Valerii
authors.forename: Giorgia
authors.initials: G
authors.lastname: Lazzarini
authors.forename: Vittorio
authors.initials: V
authors.lastname: Tomasi
authors.forename: Enzo
authors.initials: E
authors.lastname: Spisni
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D035683:MicroRNAs; D034741:RNA, Small Interfering; D051546:Cyclooxygenase 2