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Metastasis of breast tumor cells to brain is suppressed by targeting RLIP alone and in combination with 2'-Hydroxyflavanone.

Abstract：

: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), RLIP-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 RLIP-inhibition in-vivo in a novel breast tumor metastasis model and provides the rationale for further clinical investigation.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Singhal J,Singhal P,Horne D,Salgia R,Awasthi S,Singhal SS

doi

10.1016/j.canlet.2018.09.015

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

144-153

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(18)30570-6

journal_volume

438

pub_type

杂志文章

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