A Marine Anthraquinone SZ-685C Overrides Adriamycin-Resistance in Breast Cancer Cells through Suppressing Akt Signaling

被引:33
作者
Zhu, Xun [1 ,2 ,3 ]
He, Zhenjian [1 ,2 ,3 ]
Wu, Jueheng [1 ,2 ,3 ]
Yuan, Jie [1 ,2 ,4 ]
Wen, Weitao [1 ,2 ,3 ]
Hu, Yiwen [1 ,2 ,3 ]
Jiang, Yi [5 ,6 ]
Lin, Cuiji [1 ,2 ,3 ]
Zhang, Qianhui [1 ,2 ]
Lin, Min [1 ,2 ]
Zhang, Henan [1 ,2 ]
Yang, Wan [1 ,2 ]
Chen, Hong [2 ,7 ]
Zhong, Lili [2 ,7 ]
She, Zhigang [2 ,7 ]
Chen, Shengping [1 ,2 ]
Lin, Yongcheng [2 ,7 ]
Li, Mengfeng [1 ,2 ,3 ]
机构
[1] Sun Yat Sen Univ, Minist Educ, Key Lab Trop Dis Control, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Bur Educ, Guangdong Prov Key Lab Funct Mol Ocean Microorgan, Guangzhou 510080, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Microbiol, Guangzhou 510080, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Biochem, Guangzhou 510080, Guangdong, Peoples R China
[5] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Cardiol, Guangzhou 510080, Guangdong, Peoples R China
[6] First Peoples Hosp Zigong, Dept Cardiol, Zigong 643000, Peoples R China
[7] Sun Yat Sen Univ, Sch Chem & Chem Engn, Guangzhou 510275, Guangdong, Peoples R China
基金
中国博士后科学基金;
关键词
SZ-685C; breast cancer; chemoresistance; Akt; PHOSPHOINOSITIDE; 3-KINASES; MULTIDRUG-RESISTANCE; ANTHRACYCLINES; CARDIOTOXICITY; MECHANISMS; APOPTOSIS; SURVIVAL;
D O I
10.3390/md10040694
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Breast cancer remains a major health problem worldwide. While chemotherapy represents an important therapeutic modality against breast cancer, limitations in the clinical use of chemotherapy remain formidable because of chemoresistance. The HER2/PI-3K/Akt pathway has been demonstrated to play a causal role in conferring a broad chemoresistance in breast cancer cells and thus justified to be a target for enhancing the effects of anti-breast cancer chemotherapies, such as adriamycin (ADR). Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance are urgently needed for the treatment of breast cancer. In this context, SZ-685C, an agent that has been previously shown, as such, to suppress Akt signaling, is expected to increase the efficacy of chemotherapy. Our current study investigated whether SZ-685C can override chemoresistance through inhibiting Akt signaling in human breast cancer cells. ADR-resistant cells derived from human breast cancer cell lines MCF-7, MCF-7/ADR and MCF-7/Akt, were used as models to test the effects of SZ-685C. We found that SZ-685C suppressed the Akt pathway and induced apoptosis in MCF-7/ADR and MCF-7/Akt cells that are resistant to ADR treatment, leading to antitumor effects both in vitro and in vivo. Our data suggest that use of SZ-685C might represent a potentially promising approach to the treatment of ADR-resistant breast cancer.
引用
收藏
页码:694 / 711
页数:18
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