Abstract
Mammary gland tumor is the most common spontaneous tumor in intact female dogs, and its poor prognosis remains a clinical challenge. Ivermectin, a well-known anti-parasitic agent, has been implicated as a potential anticancer agent in various types of human cancer. However, there are no reports evaluating the antitumor effects of ivermectin in canine mammary tumor. Here, we investigated whether ivermectin was able to inhibit canine mammary tumor development and explored the related mechanisms. Ivermectin inhibited the growth of canine mammary tumor cell lines in a dose- and time-dependent manner. The antitumor effects induced by ivermectin were associated with cell cycle arrest at G1 phase via down-regulation of CDK4 and cyclin D1 expression, with no significant induction of apoptosis. Furthermore, significantly reduced β-catenin nuclear translocation was observed after treatment with ivermectin, resulting in the inactivation of WNT signaling. Consistent with the results in vitro, a significant suppression of tumor growth by ivermectin was observed in canine mammary tumor xenografts. Ivermectin, as a promising anti-cancer agent, inhibits the growth of canine mammary tumor by regulating cell cycle progression and WNT signaling.
References
Nov 18, 1994·Cell·C J Sherr
Apr 14, 1999·Nature·O Tetsu, F McCormick
Jun 5, 2002·Nature Reviews. Cancer·William C Hahn, Robert A Weinberg
Nov 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Martin A NowakChristoph Lengauer
Apr 21, 2005·Seminars in Cell & Developmental Biology·Irma Sánchez, Brian David Dynlacht
Dec 13, 2005·Nature·Gary DavidsonChristof Niehrs
Dec 25, 2007·Cell Cycle·Rakesh K SrivastavaSharmila Shankar
Feb 18, 2009·Cell Cycle·Irina N AlimovaAnn D Thor
Jun 1, 2006·Veterinary and Comparative Oncology·R UyamaN Sasaki
Jun 8, 2011·Reproduction in Domestic Animals = Zuchthygiene·N SleeckxL Van Brantegem
Feb 16, 2012·Cell Cycle·Daniel Cirera-SalinasCarlos Fernández-Hernando
Feb 22, 2012·Translational Research : the Journal of Laboratory and Clinical Medicine·Salomé S PinhoFátima Gärtner
May 16, 2012·Frontiers in Molecular Neuroscience·Timothy Lynagh, Joseph W Lynch
Dec 22, 2012·Nature Reviews. Cancer·Jamie N Anastas, Randall T Moon
May 7, 2013·Oncogene·Y J Choi, L Anders
Nov 6, 2013·Annual Review of Medicine·Longchuan Bai, Shaomeng Wang
Jan 1, 2011·Cancers·Kenneth C ValkenburgBart O Williams
Aug 22, 2014·EMBO Molecular Medicine·Alice MelottiAriel Ruiz i Altaba
Jun 16, 2016·Cancer Research·Qianhui DouCanhua Huang
Oct 30, 2016·Biochemical and Biophysical Research Communications·Yingying LiuBo Liu
Apr 13, 2017·BMC Cancer·Xu YangDegui Lin
Jul 12, 2017·Oncology Letters·Hongchao DuDegui Lin
Aug 30, 2017·Biochemical and Biophysical Research Communications·Min ZhuZhifang Zhou
Mar 15, 2018·Neoplasma·X ChenH Zhang
Aug 1, 2018·Trends in Cell Biology·Shom GoelJean J Zhao
Oct 13, 2018·Tissue & Cell·Hong ZhangDegui Lin
Citations
Sep 23, 2020·Journal of Cellular Physiology·Na LiXianquan Zhan
Jun 19, 2020·The EPMA Journal·Na Li, Xianquan Zhan
Aug 23, 2020·Pharmaceuticals·Gaber El-Saber BatihaAmany Magdy Beshbishy
Dec 3, 2020·Frontiers in Veterinary Science·Nan ChengDegui Lin
Oct 14, 2020·Journal of Mass Spectrometry : JMS·Na LiXianquan Zhan
Sep 25, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mingyang TangQiang Fang
Dec 31, 2020·Animals : an Open Access Journal From MDPI·Ying ZhaoDegui Lin
Mar 9, 2021·Frontiers in Veterinary Science·Guillermo ValdiviaLaura Peña
Apr 20, 2021·Frontiers in Pharmacology·Hanne-Line RabbenChun-Mei Zhao
Aug 13, 2021·The Journal of Antibiotics·Naoyuki Nishiya, Honami Yonezawa