Combination of AZD3463 and DZNep Prevents Bone Metastasis of Breast Cancer by Suppressing Akt Signaling.

Frontiers in Pharmacology
Wenxin HeAn Qin

Abstract

Osteolysis resulting from osteoclast overactivation is one of the severe complications of breast cancer metastasis to the bone. Previous studies reported that the anti-cancer agent DZNep induces cancer cell apoptosis by activating Akt signaling. However, the effect of DZNep on breast cancer bone metastasis is unknown. We previously found that DZNep enhances osteoclast differentiation by activating Akt. Therefore, we explored the use of the anti-cancer agent AZD3463 (an Akt inhibitor) along with DZNep, as AZD3463 can act as an anti-cancer agent and can also potentially ameliorate bone erosion. We evaluated osteoclast and breast cancer cell phenotypes and Akt signaling in vitro by treating cells with DZNep and AZD3463. Furthermore, we developed a breast cancer bone metastasis animal model in mouse tibiae to further determine their combined effects in vivo. Treatment of osteoclast precursor cells with DZNep alone increased osteoclast differentiation, bone resorption, and expression of osteoclast-specific genes. These effects were ameliorated by AZD3463. The combination of DZNep and AZD3463 inhibited breast cancer cell proliferation, colony formation, migration, and invasion. Finally, intraperitoneal injection of DZNep and AZD3463 ...Continue Reading

References

Jun 15, 1979·Biochemical Pharmacology·P K Chiang, G L Cantoni
Mar 1, 2002·British Journal of Cancer·G Pérez-TenorioUNKNOWN Southeast Sweden Breast Cancer Group
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Celina G KleerArul M Chinnaiyan
Oct 21, 2006·Biochemical and Biophysical Research Communications·Hao HuangHong-Hee Kim
Nov 26, 2009·Cancer Research·Mario-Luca SuvàIvan Stamenkovic
Dec 23, 2010·Future Oncology·Andrea Piunti, Diego Pasini
Dec 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jang Bae MoonNacksung Kim
Dec 22, 2011·British Journal of Cancer·C-J Chang, M-C Hung
Jan 3, 2012·International Journal of Biological Sciences·Kyung Hyun Yoo, Lothar Hennighausen
Jun 20, 2012·Current Osteoporosis Reports·Pierre J Marie
Nov 22, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David C SmithMaha Hussain
Jul 11, 2013·Critical Reviews in Oncology/hematology·Peyman HadjiMichael Gnant
Sep 6, 2013·The Journal of Biological Chemistry·Huiling CaoGuozhi Xiao
Mar 27, 2015·Neoplasia : an International Journal for Oncology Research·Gabriel N Hortobagyi
May 31, 2016·Clinical Epigenetics·Koraljka Gall TrošeljDjurdjica Ugarkovic
Jul 13, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Matthew SmithKarim Fizazi
Nov 30, 2016·Cancer Metastasis Reviews·Angel Guerrero-ZotanoCarlos L Arteaga
Dec 10, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sarah HemmingStan Gronthos
Oct 29, 2017·Calcified Tissue International·Sofia Sousa, Philippe Clézardin
Jan 9, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bernard EscudierToni K Choueiri
Feb 9, 2018·Breast Cancer Research and Treatment·Ricardo L B CostaWilliam J Gradishar
Feb 24, 2018·Cell Death & Disease·Shijie ZhengDanian Chen
Jan 17, 2019·Blood Cancer Journal·Sausan A MoharramJulhash U Kazi
Jun 7, 2019·Journal of Cancer Research and Clinical Oncology·Weiping LiangJian Zhang
Aug 11, 2019·Journal of Oral Biosciences·Shunsuke UeharaYasuhiro Kobayashi
Oct 16, 2020·Acta Pharmacologica Sinica·Xiang-Jin ZhengGuan-Hua Du

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