Astragalus polysaccharide restores autophagic flux and improves cardiomyocyte function in doxorubicin-induced cardiotoxicity

被引：117

作者：

Cao, Yuan ^{[1
]}

Shen, Tao ^{[1
]}

Huang, Xiuqing ^{[1
]}

Lin, Yajun ^{[1
]}

Chen, Beidong ^{[1
]}

Pang, Jing ^{[1
]}

Li, Guoping ^{[1
]}

Wang, Que ^{[1
]}

Zohrabian, Sylvia ^{[2
]}

Duan, Chao ^{[3
]}

Ruan, Yang ^{[4
,5
]}

Man, Yong ^{[1
]}

Wang, Shu ^{[1
]}

Li, Jian ^{[1
]}

机构：

[1] Peking Univ, Sch Clin Med 5, MOH Key Lab Geriatr, Beijing Hosp,Natl Ctr Gerontol, Beijing 100730, Peoples R China

[2] Boston Childrens Hosp, Dept Cardiol, Enders 1250, Boston, MA 02115 USA

[3] Beijing Technol & Business Univ, Beijing Key Lab Plant Resources Res & Dev, Beijing 100037, Peoples R China

[4] Capital Med Univ, Beijing Anzhen Hosp, Beijing 100029, Peoples R China

[5] Beijing Inst Heart Lung & Blood Vessel Dis, Beijing 100029, Peoples R China

来源：

ONCOTARGET | 2017年 / 8卷 / 03期

基金：

中国国家自然科学基金;

关键词：

astragalus polysaccharide; doxorubicin; cardiomyocyte; autophagy; AMPK/mTOR; SURVIVAL; PROTEIN; STRESS; DEATH; CELLS;

D O I：

10.18632/oncotarget.13596

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Doxorubicin (adriamycin), an anthracycline antibiotic, is commonly used to treat many types of solid and hematological malignancies. Unfortunately, clinical usage of doxorubicin is limited due to the associated acute and chronic cardiotoxicity. Previous studies demonstrated that Astragalus polysaccharide (APS), the extracts of Astragalus membranaceus, had strong anti-tumor activities and anti-inflammatory effects. However, whether APS could mitigate chemotherapy-induced cardiotoxicity is unclear thus far. We used a doxorubicin-induced neonatal rat cardiomyocyte injury model and a mouse heart failure model to explore the function of APS. GFP-LC3 adenovirus-mediated autophagic vesicle assays, GFP and RFP tandemly tagged LC3 (tfLC3) assays and Western blot analyses were performed to analyze the cell function and cell signaling changes following APS treatment in cardiomyocytes. First, doxorubicin treatment led to C57BL/6J mouse heart failure and increased cardiomyocyte apoptosis, with a disturbed cell autophagic flux. Second, APS restored autophagy in doxorubicin-treated primary neonatal rat ventricular myocytes and in the doxorubicin-induced heart failure mouse model. Third, APS attenuated doxorubicin-induced heart injury by regulating the AMPK/mTOR pathway. The mTOR inhibitor rapamycin significantly abrogated the protective effect of APS. These results suggest that doxorubicin could induce heart failure by disturbing cardiomyocyte autophagic flux, which may cause excessive cell apoptosis. APS could restore normal autophagic flux, ameliorating doxorubicin-induced cardiotoxicity by regulating the AMPK/mTOR pathway.

引用

页码：4837 / 4848

页数：12

共 32 条

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