Fluvastatin Prevents Lung Adenocarcinoma Bone Metastasis by Triggering Autophagy
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Date
2017
Author(s)
Yang, Zuozhang
Su, Zhenyi
DeWitt, Judy Park
Xie, Lin
Chen, Yongbin
Li, Xiaojuan
Han, Lei
Li, Dongqi
Xia, Junfeng
Zhang, Ya
Yang, Yihao
Jin, Congguo
Zhang, Jing
Li, Su
Li, Kun
Zhang, Zhiping
Qu, Xin
He, Zewei
Chen, Yanjin
Shen, Yan
Ren, Mingyan
Yuan, Zhongqin
Publisher
Elsevier
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Citation
Yang, Z., Z. Su, J. P. DeWitt, L. Xie, Y. Chen, X. Li, L. Han, et al. 2017. “Fluvastatin Prevents Lung Adenocarcinoma Bone Metastasis by Triggering Autophagy.” EBioMedicine 19 (1): 49-59. doi:10.1016/j.ebiom.2017.04.017. http://dx.doi.org/10.1016/j.ebiom.2017.04.017.
Abstract
Bone is one of the most preferred sites of metastasis in lung cancer. Currently, bisphosphonates and denosumab are major agents for controlling tumor-associated skeletal-related events (SREs). However, both bisphosphonates and denosumab significantly increase the risk for jaw osteonecrosis. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and the most frequently prescribed cholesterol-lowering agents, have been reported to inhibit tumor progression and induce autophagy in cancer cells. However, the effects of statin and role of autophagy by statin on bone metastasis are unknown. In this study, we report that fluvastatin effectively prevented lung adenocarcinoma bone metastasis in a nude mouse model. We further reveal that fluvastatin-induced anti-bone metastatic property was largely dependent on its ability to induce autophagy in lung adenocarcinoma cells. Atg5 or Atg7 deletion, or 3-methyadenine (3-MA) or Bafilomycin A1 (Baf A1) treatment prevented the fluvastatin-induced suppression of bone metastasis. Furthermore, we reveal that fluvastatin stimulation increased the nuclear p53 expression, and fluvastatin-induced autophagy and anti-bone metastatic activity were mostly dependent on p53.
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