机构：[1]Departments of The Second Medical Oncology,The 3rd Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, China[2]Departments of The Second Thoracic Surgery,The 3rd Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, China[3]Departments of Breast Surgery, The 3rd Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, China[4]Department of Urology, Changhai Hospital, Navy Medical University (Second Military Medical University), Shanghai, China[5]Department of Otolaryngology, Head and Neck Surgery, Kunming Children’s Hospital, Kunming, China[6]SDIVF R&D Center, Hong Kong Science Park, Sha Tin, New Territories, Hong Kong[7]CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong[8]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China[9]School of Public Health, Kunmming Medical University, Kunming, Yunnan, China[10]Department of Urology, The 1st Affiliated Hospital of Kunming Medical University, Kunming, China昆明医科大学附属第一医院[11]Institute of Medical and Pharmaceutical Sciences, The Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
Activation of the phosphoinositide 3 kinase (PI3K)/AKT pathway is frequently implicated in resistance to anti cancer therapies. PI3K inhibitors can restore sensitivity to standard breast cancer therapies, including endocrine therapy, HER2-targeted agents, and chemotherapy. Our previous research showed that econazole, a novel PI3Ka Inhibitor, inhibits the PI3K/AKT pathway and induces apoptosis in lung cancer cells. In this study, econazole showed significant cytotoxic activity against Adriamycin-resistant breast cancer cells in vitro and in vivo. Additionally, econazole significantly sensitized MDA-MB-231 and MCF-7 cells to Adriamycin via inhibiting the PI3K/AKT pathway. Overexpression of constitutively active AKT1 abolished the function of econazole. The combination of econazole and Adriamycin exerted synergistic inhibitory effects in breast cancer cells in vitro and in vivo. Taken together, the PI3K inhibitor econazole could effectively overcome Adriamycin resistance and showed synergistic effects with chemotherapy on breast cancer.
基金：
This study was supported in part by grants from National Key R&D Program of China (2018-YFC2000400), the National Nature Science Foundation of China (81830087, U1602221 and 31771516 to Chen, C.) and Science and Technology Innovation Team of Yunnan Province (2018HC002 to Liu, R.), top young talents of ten thousand talents plan in Yunnan Province (2019), the medical reserve personnel training program of Yunnan province (H-201609), the General Research Projects in Yunnan Province (2019FB113), Health Science and technology project of Yunnan province (2018NS0052), the Hundred-Talent Program of Kunming Medical University (60118260119) and the Joint Application Project from the Yunnan Provincial Science and Technology Department (2019), Yunnan Province Science and Technology Department-Kunming Medical University Joint Fund for Fundamental Research (2019FE0-01-064, 2019FE001-082).
第一作者机构：[1]Departments of The Second Medical Oncology,The 3rd Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, China
共同第一作者：
通讯作者：
通讯机构：[8]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China[11]Institute of Medical and Pharmaceutical Sciences, The Academy of Medical Science, Zhengzhou University, Zhengzhou, China.[*1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiaochang East Road, Kunming 650223, Yunnan, China.[*2]Institute of Medical and Pharmaceutical Sciences, The Academy of Medical Science, Zhengzhou University, Science Avenue 100, Zhengzhou 450001, Henan, China.
推荐引用方式(GB/T 7714)：
Chao Dong,Yin Chen,Jing Ma,et al.Econazole nitrate reversed the resistance of breast cancer cells to Adriamycin through inhibiting the PI3K/AKT signaling pathway[J].AMERICAN JOURNAL OF CANCER RESEARCH.2020,10(1):263-274.
APA：
Chao Dong,Yin Chen,Jing Ma,Runxiang Yang,Hongjian Li...&Ceshi Chen.(2020).Econazole nitrate reversed the resistance of breast cancer cells to Adriamycin through inhibiting the PI3K/AKT signaling pathway.AMERICAN JOURNAL OF CANCER RESEARCH,10,(1)
MLA：
Chao Dong,et al."Econazole nitrate reversed the resistance of breast cancer cells to Adriamycin through inhibiting the PI3K/AKT signaling pathway".AMERICAN JOURNAL OF CANCER RESEARCH 10..1(2020):263-274
