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

Wanqiong Yuan; Bao Hai; Xiaoqing Ren; Junxiong Zhu; Chenggui Zhang; Zhiyuan Guan; Jialin Jia; Hong Wang; Baoshan Cao; Chunli Song

doi:10.1016/j.tranon.2020.100867

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

Transl Oncol. 2020 Dec;13(12):100867. doi: 10.1016/j.tranon.2020.100867. Epub 2020 Sep 18.

Authors

Wanqiong Yuan¹, Bao Hai², Xiaoqing Ren³, Junxiong Zhu⁴, Chenggui Zhang⁵, Zhiyuan Guan⁶, Jialin Jia⁷, Hong Wang⁸, Baoshan Cao⁹, Chunli Song¹⁰

Affiliations

¹ Department of Orthopedics, Peking University Third Hospital, Beijing Key Laboratory of Spinal Disease, Beijing, China. Electronic address: yuanwanqiong@bjmu.edu.cn.
² Department of Orthopedics, Peking University Third Hospital, Beijing Key Laboratory of Spinal Disease, Beijing, China. Electronic address: haibao@bjmu.edu.cn.
³ Department of Pharmacy, Peking University Third Hospital, Beijing, China.
⁴ Department of Orthopedics, Peking University Third Hospital, Beijing Key Laboratory of Spinal Disease, Beijing, China. Electronic address: 1611110342@bjmu.edu.cn.
⁵ Department of Orthopedics, Peking University Third Hospital, Beijing Key Laboratory of Spinal Disease, Beijing, China. Electronic address: chenggui1214@pku.edu.cn.
⁶ Department of Orthopedics, Peking University Third Hospital, Beijing Key Laboratory of Spinal Disease, Beijing, China. Electronic address: Gzy_2008@bjmu.edu.cn.
⁷ Department of Orthopedics, Peking University Third Hospital, Beijing Key Laboratory of Spinal Disease, Beijing, China. Electronic address: jlshunli@bjmu.edu.cn.
⁸ Department of Orthopedics, Peking University Third Hospital, Beijing Key Laboratory of Spinal Disease, Beijing, China.
⁹ Department of Tumor Chemotherapy and Radiation Sickness, Peking University Third Hospital, Beijing, China.
¹⁰ Department of Orthopedics, Peking University Third Hospital, Beijing Key Laboratory of Spinal Disease, Beijing, China. Electronic address: schl@bjmu.edu.cn.

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.