摘要
事实上,磷脂酰肌醇-3-激酶(PI3K)信号通路是一种最常见的失调的信号转导网络,其引发了PI3K信号通路抑制剂的发生强度。然而,最近的临床试验数据表明PI3K抑制剂在耐受剂量下只有有限的活性。因此,迫切需要确定合理的联合治疗法以提高PI3K靶向治疗肿瘤的疗效。在这项研究中,我们研究了膳食化合物鞣花酸(EA)可以提高PI3K抑制剂GDC-0941在乳腺癌中的治疗效果。特别是,使用一组乳腺癌细胞系,结果表明,联合使用EA和GDC-0941在连接和分离条件下能明显抑制细胞生长,能阻止肿瘤体外的迁移和侵袭,以及体内的发生和转移。此外,我们发现,EA可促进细胞凋亡,并进一步降低GDC-0941处理过的乳腺癌细胞中AKT/mTOR的活化。同时,我们的数据表明,EA可能是一种安全有效的剂促进PI3K定向的乳腺癌的治疗。这种药物的组合可能值得进行进一步临床研究。
关键词: 乳腺癌,联合治疗,鞣花酸,GDC-0941,磷脂酰肌醇-3-激酶,靶向治疗。
Current Molecular Medicine
Title:Ellagic Acid Enhances the Efficacy of PI3K Inhibitor GDC-0941 in Breast Cancer Cells
Volume: 15 Issue: 5
Author(s): L. Shi, X. Gao, X. Li, N. Jiang, F. Luo, C. Gu, M. Chen, H. Cheng and P. Liu
Affiliation:
关键词: 乳腺癌,联合治疗,鞣花酸,GDC-0941,磷脂酰肌醇-3-激酶,靶向治疗。
摘要: 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.
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Cite this article as:
L. Shi, X. Gao, X. Li, N. Jiang, F. Luo, C. Gu, M. Chen, H. Cheng and P. Liu , Ellagic Acid Enhances the Efficacy of PI3K Inhibitor GDC-0941 in Breast Cancer Cells, Current Molecular Medicine 2015; 15 (5) . https://dx.doi.org/10.2174/1566524015666150505161046
DOI https://dx.doi.org/10.2174/1566524015666150505161046 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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