Journal
CURRENT MOLECULAR MEDICINE
Volume 15, Issue 5, Pages 478-486Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1566524015666150505161046
Keywords
Breast cancer; combination therapy; ellagic acid; GDC-0941; PI3K; targeted therapy
Categories
Funding
- National Natural Science Foundation of China [81372853, 81472447]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT13049]
- Liaoning Provincial Natural Science Foundation of China [502537]
- Liaoning Provincial Climbing Scholars Supporting Program of China
- Institute of Cancer Stem Cell, Dalian Medical University
- Cancer Institute at Second Affiliated Hospital of Dalian Medical University
Ask authors/readers for more resources
The fact that the phosphatidylinositol 3 kinase (PI3K) signaling pathway is one of the most frequently deregulated signaling networks has triggered intensive efforts in the development of PI3K pathway inhibitors. However, recent clinical trial data have shown only limited activity of PI3K inhibitors at tolerated doses. Thus, there is an urgent need to identify rational combination therapy to improve the efficacy of PI3K-targeted cancer treatment. In this study, we investigated if dietary compound ellagic acid (EA) could improve the therapeutic efficacy of PI3K inhibitor GDC-0941 in breast cancer. Specifically, using a panel of breast cancer cell lines, we showed that combined use of EA and GDC-0941 significantly inhibited cell growth under attached and detached conditions, blocked migration and invasion in vitro as well as tumor initiation and metastasis in vivo. Furthermore, we found that EA promoted apoptosis and further reduced AKT/mTOR activation in GDC-0941-treated breast cancer cells. Together, our data suggest that EA may be a safe and effective agent to boost the efficacy of PI3K-directed breast cancer therapy and that such drug combination may merit further clinical investigation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available