Knockdown of heme oxygenase-1 promotes apoptosis and autophagy and enhances the cytotoxicity of doxorubicin in breast cancer cells

被引：38

作者：

Zhu, Xiao-Feng ^{[1
]}

Li, Wen ^{[2
,3
]}

Ma, Jie-Yi ^{[2
]}

Shao, Nan ^{[1
]}

Zhang, Yun-Jian ^{[1
]}

Liu, Rui-Ming ^{[2
,3
]}

Wu, Wei-Bin ^{[1
]}

Lin, Ying ^{[1
]}

Wang, Shen-Ming ^{[1
,3
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Guangzhou 510080, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Affiliated Hosp 1, Lab Gen Surg, Guangzhou 510080, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Affiliated Hosp 1, Guangdong Engn Lab Diag & Treatment Vasc Dis, Guangzhou 510080, Guangdong, Peoples R China

来源：

Oncology Letters | 2015年 / 10卷 / 05期

基金：

中国国家自然科学基金;

关键词：

heme oxygenase-1; apoptosis; autophagy; doxorubicin; breast cancer; chemoresistance; NITRIC-OXIDE; TUMOR-GROWTH; DEATH; RESISTANCE; EXPRESSION; SURVIVAL; GENE; OVEREXPRESSION; MACROAUTOPHAGY; ACTIVATION;

D O I：

10.3892/ol.2015.3735

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Heme oxygenase-1 (HMOX-1) is a microsomal enzyme that exerts anti-apoptotic and cytoprotective effects. In the present study, HMOX-1 was demonstrated to be over-expressed and able to be induced by doxorubicin in breast cancer cell lines. Knockdown of HMOX-1 using short interfering ( si) RNA enhanced the cytotoxicity of doxorubicin in MDA-MB-231 and BT549 cells. Knockdown of HMOX-1 downregulated B cell lymphoma (Bcl)-2 and Bcl-extra large expression, and significantly enhanced doxorubicin-induced apoptosis in MDA-MB-231 and BT549 cells. Additionally, knockdown of HMOX-1 upregulated light chain 3B expression and markedly increased the accumulation of autophagic vacuoles in MDA-MB-231 and BT549 cells treated with doxorubicin. These results indicated that HMOX-1 may be involved in conferring the chemoresistance of breast cancer cells, by preventing apoptosis and autophagy. Therefore, HMOX-1 may represent a potential therapeutic target for enhancing the cytotoxicity and efficacy of doxorubicin during the treatment of breast cancer.

引用

页码：2974 / 2980

页数：7

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