期刊
CANCER LETTERS
卷 438, 期 -, 页码 144-153出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.09.015
关键词
RLIP; Breast cancer; Phytochemicals; Brain metastasis; Chemotherapeutics
类别
资金
- Department of Defense grant [W81XWH-16-1-0641]
- Beckman Research Institute, City of Hope
- Department of Medical Oncology at City of Hope
Brain metastasis is an important cause of morbidity and mortality in cancer-patients. Breast tumor cells frequently metastasize to brain and initiate severe therapeutic complications. In the present study, we evaluated the anti-metastatic effects of 2'-hydroxyflavanone (2HF) alone and in combination with RLIP targeted therapy in a novel murine model of breast tumor metastasis. The MDA-MB231Br (brain-seeking) breast cancer (BC) cells stably-transfected with luciferase were injected into the left-ventricle of NSG mouse heart and the migration of cells to brain was monitored using a non-invasive bioluminescent imaging system. To evaluate the tumor growth suppressive effects, mice were given 2HF (50 mg/kg, b.w., alternate days orally), BLIP-antibody (Rab; 5 mg/kg, b.w., weekly i.p.) or combination of 2HF + Rab starting day1 after intra-cardiac injection. Our results reveal that 2HF and Rab significantly prevented the metastasis of BC cells to brain. Further, mice treated with combination of 2HF + Rab exhibited no metastasis as compared to either or the single agent-treated mice. This study for the first time demonstrates the anti-metastatic effects of 2HF and BLIP-inhibition in-vivo in a novel breast tumor metastasis model and provides the rationale for further clinical investigation.
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