期刊
CLINICAL CANCER RESEARCH
卷 21, 期 9, 页码 2127-2137出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-2279
关键词
-
类别
资金
- Department of Defense [W81XWH-09-1-0212]
- NIH [U54CA143837, U54CA151668, P50 CA083639]
- CPRIT from the State of Texas [RP121071]
- RGK Foundation
- Gilder Foundation
- Betty Anne Asche Murray Distinguished Professorship
- John Q. Gaines Foundation Professorship for Cancer Research
- [NCI-U54CA096300]
- [NCI-P50PKCA093459]
- [CA151668]
- [CA180145]
- [NCI-CA151668]
- [NCI-UH2TR00943]
Purpose: Zoledronic acid is being increasingly recognized for its antitumor properties, but the underlying functions are not well understood. In this study, we hypothesized that zoledronic acid inhibits ovarian cancer angiogenesis preventing Rac1 activation. Experimental Design: The biologic effects of zoledronic acid were examined using a series of in vitro [cell invasion, cytokine production, Rac1 activation, reverse-phase protein array, and in vivo (orthotopic mouse models)] experiments. Results: There was significant inhibition of ovarian cancer (HeyA8-MDR and OVCAR-5) cell invasion as well as reduced production of proangiogenic cytokines in response to zoledronic acid treatment. Furthermore, zoledronic acid inactivated Rac1 and decreased the levels of Pak1/p38/matrix metalloproteinase-2 in ovarian cancer cells. In vivo, zoledronic acid reduced tumor growth, angiogenesis, and cell proliferation and inactivated Rac1 in both HeyA8-MDR and OVCAR-5 models. These in vivo antitumor effects were enhanced in both models when zoledronic acid was combined with nab-paclitaxel. Conclusions: Zoledronic acid has robust antitumor and anti-angiogenic activity and merits further clinical development as ovarian cancer treatment. (C) 2015 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据