ETAR antagonist ZD4054 exhibits additive effects with aromatase inhibitors and fulvestrant in breast cancer therapy, and improves in vivo efficacy of anastrozole

Breast Cancer Research and Treatment
M SmollichP Wülfing

Abstract

Endothelin-1 (ET-1) and endothelin A receptor (ETAR) contribute to the development and progression of breast carcinomas by modulating cell proliferation, angiogenesis, and anti-apoptosis. We investigated antitumoral effects of the specific ETAR antagonist ZD4054 in breast cancer cells and xenografts, and assessed antitumoral efficacy of the combinations of ZD4054 with aromatase inhibitors and fulvestrant. Gene expression changes were assessed by quantitative real-time PCR. Cell proliferation was measured using alamarBlue; migration and invasion assays were performed using modified Boyden chambers. Evaluating the antitumoral efficacy of ZD4054 in vivo, different breast cancer models were employed using nude mice xenografts. ZD4054 reduced ET-1 and ETAR expression in MCF-7, MDA-MB-231, and MDA-MB-468 breast cancer cells in a concentration-dependent manner. ZD4054 inhibited invasion by up to 37.1% (P = 0.022). Combinations of ZD4054 with either anastrozole or letrozole produced significant reductions in migration of aromatase-overexpressing MCF-7aro cells (P < 0.05). Combination of ZD4054 with fulvestrant reduced MCF-7 cell migration and invasion by 36.0% (P = 0.027) and 56.7% (P < 0.001), respectively, with effects significantly ...Continue Reading

References

Apr 1, 1992·The American Journal of Physiology·Y LiuA W Jones
Sep 1, 1974·Journal of the National Cancer Institute·R CailleauW J Reeves
Feb 1, 1995·British Journal of Pharmacology·F Pérez-VizcaínoT D Warner
Apr 1, 1993·Physiological Reviews·M S Simonson
May 23, 1998·The Biochemical Journal·A K MoreyE R Levin
Jun 20, 1998·The Journal of Biological Chemistry·M OkazawaT Masaki
Mar 16, 2001·Breast Cancer Research : BCR·M J DuffyN O'Higgins
Jun 21, 2002·European Urology·Mirtha GrandeMargareta Faxén
Aug 3, 2002·Nature Reviews. Cancer·Ann F ChambersIan C MacDonald
Aug 24, 2002·Clinical Science·Laura RosanòAnna Bagnato
Sep 5, 2003·American Journal of Physiology. Renal Physiology·Andrey Sorokin, Donald E Kohan
Nov 19, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Angela H BrodieBrian Long
Jan 23, 2004·The Journal of Asthma : Official Journal of the Association for the Care of Asthma·A Dosanjh, B Zuraw
Jan 24, 2004·Apoptosis : an International Journal on Programmed Cell Death·P Mehlen, D E Bredesen
Apr 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pia WülfingLudwig Kiesel
Aug 21, 2004·Breast Cancer Research and Treatment·Karin Milde-LangoschAna-Maria Bamberger
Mar 23, 2005·Biochimie·Uta B HofmannJürgen C Becker
Aug 2, 2005·Cancer Science·Daisuke YamazakiTadaomi Takenawa
Aug 2, 2005·Biochimica Et Biophysica Acta·Makoto SumitomoDavid M Nanus
Aug 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Norikazu MizunoHiroshi Itoh
Feb 3, 2006·American Journal of Physiology. Cell Physiology·Johanna MilanRaphael Zidovetzki
Apr 6, 2006·The Journal of Biological Chemistry·Yang ZhengDavid A Foster
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael A Carducci, Antonio Jimeno
Nov 2, 2006·The British Journal of Surgery·K GrantM Loizidou
Feb 14, 2007·Breast Cancer Research and Treatment·Martin SmollichPia Wülfing
May 1, 2007·Breast Cancer Research and Treatment·M SmollichP Wülfing
May 19, 2007·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Manit AryaHiten R H Patel
Nov 23, 2007·European Journal of Pharmacology·David NilssonMalin Malmsjö
Mar 8, 2008·The International Journal of Biochemistry & Cell Biology·Anna Bagnato, Laura Rosanò
Sep 2, 2008·Expert Review of Anticancer Therapy·Martin Smollich, Pia Wülfing

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Citations

Jul 12, 2013·ISRN Oncology·Deimante TamkusNikolay V Dimitrov
Mar 15, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Vasileios KallesAntonia Gounaris
Sep 17, 2013·Critical Reviews in Oncology/hematology·Soussan IraniAlfred King-Yin Lam
Jan 22, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Rong Wang, Roderick H Dashwood
Jan 4, 2012·Journal of Surgical Oncology·Paraskevi LiakouGeorge Z Rassidakis
Oct 22, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Jacqueline A Clarkson-JonesHelen Swaisland
Aug 1, 2012·Life Sciences·Neveen Said, Dan Theodorescu
Dec 6, 2018·International Journal of Molecular Sciences·Rosamaria LappanoMarcello Maggiolini
Jan 5, 2011·Nature Reviews. Drug Discovery·Rosamaria Lappano, Marcello Maggiolini

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