Abstract
Pyrotinib (PYR) is a pan-HER kinase inhibitor that inhibits signaling via the RAS/RAF/MEK/MAPK and PI3K/AKT pathways. In this study, we aimed to investigate the antitumor efficacy of pyrotinib combined with adriamycin (ADM) and explore its mechanisms on HER2+ breast cancer. We investigated the effects of PYR and ADM on breast cancer in vitro and in vivo. MTT assay, Wound-healing, and transwell invasion assays were used to determine the effects of PYR, ADM or PYR combined with ADM on cell proliferation, migration, and invasion of SK-BR-3 and AU565 cells in vitro. Cell apoptosis and cycle were detected through flow cytometry. In vivo, xenograft models were established to test the effect of PYR, ADM, or the combined therapy on the nude mice. Western blotting was performed to assess the expression of Akt, p-Akt, p-65, p-p65, and FOXC1. The results indicated that PYR and ADM significantly inhibited the proliferation, migration, and invasion of SK-BR-3 and AU565 cells, and the inhibitory rate of the combination group was higher than each monotherapy group. PYR induced G1 phase cell-cycle arrest, while ADM induced G2 phase arrest, while the combination group induced G2 phase arrest. The combined treatment showed synergistic anticancer...Continue Reading
References
Jan 1, 1984·Advances in Enzyme Regulation·T C Chou, P Talalay
Jul 16, 1981·The New England Journal of Medicine·R C YoungC E Myers
Jan 31, 1997·Science·H DudekM E Greenberg
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·L LingD V Goeddel
May 23, 1998·Annual Review of Immunology·S GhoshE B Kopp
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
May 11, 2002·Nature Reviews. Cancer·Michael KarinZhi-Wei Li
Jan 30, 2004·Molecular and Cellular Biology·Marnie S RobertsJim C Norman
Oct 14, 2004·British Journal of Cancer·D M Abd El-RehimI O Ellis
Dec 29, 2006·The New England Journal of Medicine·Charles E GeyerDavid Cameron
Oct 19, 2007·Nature Reviews. Cancer·Stephen S Myatt, Eric W-F Lam
May 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Han C Dan, Albert S Baldwin
Apr 22, 2010·Cancer Research·Partha S RayXiaojiang Cui
Jan 27, 2011·BMC Cancer·Caterina Peraldo-NeiaMassimo Aglietta
Aug 23, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Limin XiaKaichun Wu
Oct 2, 2012·The New England Journal of Medicine·Sunil VermaUNKNOWN EMILIA Study Group
Dec 18, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lei WangJun-Ying Xu
Dec 25, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Long-Xiao WeiMeng-Hui Yuan
Jan 16, 2013·Chemotherapy Research and Practice·Zahi MitriRuth O'Regan
Mar 8, 2013·The Surgical Clinics of North America·Leonel F Hernandez-Aya, Ana M Gonzalez-Angulo
Apr 23, 2013·The Lancet Oncology·Sandra M SwainJosé Baselga
Oct 9, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonio C WolffUNKNOWN College of American Pathologists
Dec 17, 2014·Molecular Biology International·Mehvish ShowkatKhurshid I Andrabi
May 28, 2016·British Journal of Clinical Pharmacology·Prabhjot S MundiKevin Kalinsky
Jan 25, 2017·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Xin LiLianshan Zhang
May 13, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Fei MaBinghe Xu
Jun 21, 2017·Cell Communication and Signaling : CCS·Stacey ChungXiaojiang Cui
Sep 9, 2017·Drugs·Emma D Deeks
Sep 26, 2017·The Lancet Oncology·Elizabeth Gourd
May 23, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Neelima DenduluriSharon H Giordano
Sep 13, 2018·CA: a Cancer Journal for Clinicians·Freddie BrayAhmedin Jemal
Oct 21, 2018·Drugs·Hannah A Blair
Jan 1, 2019·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Y WangF R Hirsch
Jan 25, 2019·Cancer Letters·Kai ZhangShusen Wang
May 30, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qiao LiBinghe Xu
Aug 21, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Fei MaBinghe Xu
Jan 21, 2020·Frontiers in Oncology·Le-Tian HuangCheng-Bo Han