Augmenting Tumor-Starvation Therapy by Cancer Cell Autophagy Inhibition

被引:120
作者
Yang, Bowen [1 ,2 ]
Ding, Li [1 ]
Chen, Yu [1 ,2 ]
Shi, Jianlin [1 ,2 ]
机构
[1] Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai 200050, Peoples R China
[2] Univ Chinese Acad Sci, Ctr Mat Sci & Optoelect Engn, Beijing 100049, Peoples R China
基金
国家重点研发计划; 美国国家科学基金会; 上海市自然科学基金; 中国国家自然科学基金;
关键词
autophagy; black phosphorus; glycolysis; nanomedicine; tumor-starvation therapy; 2-DEOXY-D-GLUCOSE; GLYCOLYSIS; METABOLISM; INDUCTION; 2-DEOXYGLUCOSE;
D O I
10.1002/advs.201902847
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
It was recently recognized that cancer therapeutic efficacy may be greatly compromised by an intrinsic protective mechanism called autophagy, by which cancer cells survive in harsh conditions such as starvation. Here, a synergetic strategy is described for cancer treatment by suppressing such a protective mechanism for augmenting tumor-starvation therapy. The synergetic therapy is achieved by restraining glucose metabolism using an antiglycolytic agent to predispose cancer cells to severe energy deprivation; concurrently the downstream autophagic flux and compensatory energy supplies are blocked by the autophagy inhibitor black phosphorus nanosheet. Cancer cells fail to extract their own nutrient to feed themselves, finally succumbing to therapeutic interventions and starving to death. Both in vitro and in vivo results evidence the cooperative effect between the autophagy inhibitor and antiglycolytic agent, which leads to remarkable synergetic antineoplastic outcome. It is expected that such a combinational approach by concurrently blocking exogenous and endogenous nutrition supplies will be beneficial to the design of effective tumor-specific cancer therapies in the future.
引用
收藏
页数:11
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