Naslov
Cyclopamine and tamoxifen should not be used together for treatment of breast cancer

Autori
Sabol, Maja ; Užarević, Zvonimir ; Car, Diana ; Levanat, Sonja

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

Izvornik
Hh-Gli Signalling in Development, Regeneration and Cancer / Ruiz i Altaba, Ariel ; Delidakis, Christos - : Accelopment AG, 2011, 58-58

Skup
1st HEALING International Meeting on Hh-Gli Signalling

Mjesto i datum
Kolymvari, Grčka, 23.06.2011. - 25.06.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Hedgehog signaling; cyclopamine; tamoxifen; breast cancer

Sažetak
It has been demonstrated that the Hedgehog signaling pathway may be one of the targets for treatment of breast cancer. Therefore, we decided to test the effects of combined treatment of Tamoxifen, a commonly used breast cancer therapeutic which inhibits estrogen receptor, toghether with Cyclopamine, the Hedgehog pathway inhibitor. First, we determined the effect of Tamoxifen on two different breast cancer cell lines: MCF-7, which is estrogen receptor positive (ER+), and SkBr3, which is estrogen receptor negative (ER–). As expected, Tamoxifen caused a decrease in cell viability, which was more pronounced in ER+ cell line, compared to ER– cell line. Hedgehog signaling pathway proteins (Ptch, Smo, Gli1, Shh, SuFu) were detected on both mRNA and protein level in both cell lines, although Gli1 gene expression was barely detectable in ER– cell line. Cyclopamine treatment of these cells caused a decrease in viability, which was more pronounced in the ER+ cell line. On the other hand, induction of the pathway with exogenous Shh protein induced proliferation of these cells, with a more pronounced effect on ER– cell line. Combined treatment with Cyclopamine and Tamoxifen demonstrated an unexpected result in ER+ cell line: the survival of the cells was dramatically increased compared to either treatment alone, suggesting that the combination of these two drugs somehow enables cell survival. This effect was the opposite in ER– cell line, where combined treatment reduced cell survival. Combined treatment induced the Hedgehog pathway gene expression in ER+ cells, and downregulated it in ER– cell line. Transwell migration assay showed a similar effect on ER+ cell line, with reduced migration with either Cyclopamine or Tamoxifen alone, which recovers to control levels when these two compounds are used together. These results suggest that the combined treatment with Tamoxifen and Cyclopamine may be very dangerous to use in patients, especially patients with ER+ tumors. Further research in this area is vital before any application in clinic.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA