Naslov
Indomethacin and Wnt Signalling in HT-29 Colon Cancer Cells

Autori
Kapitanović, Sanja ; Čačev, Tamara ; Antica, Mariastefania ; Kralj, Marijeta ; Cavrić, Gordana ; Pavelić, Krešimir ; Spaventi, Radan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 13th European Cancer Conference 2005 : ECCO 13 in European Journal of Cancer Supplements / Smyth, John - Pariz : Elsevier, 2005, 186-186

Skup
European Cancer Conference 2005 : ECCO 13 (13 ; 2005)

Mjesto i datum
Pariz, Francuska, 30.10.2005. - 03.11.2005

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
indomethacin; Wnt signalling; colon cancer

Sažetak
Nonsteroidal anti-inflammatory drugs (NSAIDs) lower the incidence of and mortality from colon cancer. Although there is much evidence from epidemiological and laboratory studies that NSAIDs have antitumor activity and reduce the incidence of colon cancer, the mechanism of action remains unknown. In this paper, we present the effect of indomethacin on growth inhibition, induction of apoptosis, and alterations in the expression of several genes involved in Wnt signalling in HT-29 colon cancer cells. We have shown that indomethacin reduces the proliferation rate of HT-29 colon cancer cells and induces apoptosis. Concentrations of indomethacin from 10^-4 to 10^-3 M strongly inhibited the growth of HT-29 cells. The inhibition of growth, as well as induction of apoptosis was dose and time dependent. The treatment of cells with 4×10^-4 M indomethacin caused strong inhibition of cell growth (about 70%), enhanced expression of APC, decreased expression of beta-catenin and induced expression of E-cadherin proteins. Expression of beta-catenin was not markedly reduced instead, beta-catenin was translocated from the nucleus and cytoplasm to the plasma membrane. These results were confirmed by real-time RT-PCR analysis on mRNA level. At a concentration of 4×10^-4 M indomethacin there was increased expression of APC gene (10.9-fold induction ; delta delta Ct = 3.43) and E-cadherin gene (3.5-fold induction ; delta delta Ct = 1.79). These results suggest the antiproliferative effect of indomethacin may contribute to enhanced cell adhesion through increased expression of E-cadherin and translocation of beta-catenin from the nucleus to the cell membrane

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

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