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Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization.


ABSTRACT: Tumor vessels play important roles in cancer development and angiogenesis has been characterized as an essential process for tumor cell tumor growth. Our previous studies found that a single-dose local intraosseous simvastatin injection rapidly and long-termly mobilized bone marrow-derived endothelial progenitor cells to peripheral blood, promoting angiogenesis and ameliorating ischemia injury. However, whether intraosseous injection of simvastatin participates in cancer progression and the role of angiogenesis enhancement in this process remain unknown. In this study, we found that intraosseous injection of simvastatin improves tumor vascular structure, along with increasing the percentage of pericyte coverage on tumor vessels, and reducing vascular permeability, tumor hypoxia and tumor necrosis. Further, we demonstrate that a single-dose local intraosseous simvastatin injection suppresses tumor growth, facilitates sensitivity of chemotherapy and prolongs survival in breast cancer-bearing mice. In addition, oral application, intravenous, subcutaneous and intraperitoneal injection of simvastatin do not show these effects. Taken together, these results demonstrate that intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization, which might be a promising strategy for cancer treatment.

SUBMITTER: Yuan W 

PROVIDER: S-EPMC7509234 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization.

Yuan Wanqiong W   Hai Bao B   Ren Xiaoqing X   Zhu Junxiong J   Zhang Chenggui C   Guan Zhiyuan Z   Jia Jialin J   Wang Hong H   Cao Baoshan B   Song Chunli C  

Translational oncology 20200918 12


Tumor vessels play important roles in cancer development and angiogenesis has been characterized as an essential process for tumor cell tumor growth. Our previous studies found that a single-dose local intraosseous simvastatin injection rapidly and long-termly mobilized bone marrow-derived endothelial progenitor cells to peripheral blood, promoting angiogenesis and ameliorating ischemia injury. However, whether intraosseous injection of simvastatin participates in cancer progression and the role  ...[more]

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