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

Marine Drugs

Xun Zhu²  Zhenjian He²  Jueheng Wu²  Jie Yuan²  Weitao Wen²  Yiwen Hu²  Yi Jiang³  Cuiji Lin²  Qianhui Zhang²  Min Lin²  Henan Zhang²  Wan Yang²  Hong Chen¹  Lili Zhong¹  Zhigang She¹  Shengping Chen²  Yongcheng Lin¹ 

[1] Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China;Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China;Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou 510080, China;

关键词: SZ-685C;    breast cancer;    chemoresistance;    Akt;   

DOI  :  10.3390/md10040694

来源: mdpi

【 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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.