MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy  

出　　处：《中国药理学通报》2015年第B11期243-243,共1页Chinese Pharmacological Bulletin

摘　　要：Aim Breast cancer is one of the lethal gynecological malignancy in the world. Tamoxifen （TAM） and fulvestrant （FUL） are the major drugs for patients with estrogen receptor-positive （ER ＋ ） breast cancers. Howev- er, the development of endocrine resistance is the impediment for successful treatment. In this study, we explored the mechanisms of endocrine resistance and therapeutic strategy for overcoming resistance against TAM and FUL. Methods The experiments were performed in Ell ＋ and estrogen/TAM-sensitive MCF7 cells and antiestrogen-re- sistant MCF7/LCC9 cells. Western blot and confocal microscopy were used to determine cell autophagy. Cell trans- fection and luciferase activity assay were performed to identify the target gene of miR-214. Results It showed that 4-OHT/FUL treatment induced apoptosis as well as autophagy in breast cancer cells. The increase of autophagy might be the major cause of endocrine resistance to 4-OHT or FUL. Mill-214 increased the sensitivity of breast cancer cells to the 4-OHT/FUL-induced apoptosis through inhibition of autophagy. Importantly, a negative correla- tion was established between miR-214 and UCP2 in human breast cancer tissue specimens by RT-qPCR assay. UCP2 was identified to be a direct target of mill-214. Further study in MCF7/LCC9 cells indicated that endocrine resistance might arise from activation of the PI3 K-Akt-mTOll pathway, thereby inducing autophagy by overexpres- sion of UCP2. Conclusions MiR-214 increased the sensitivity of breast cancer cells to TAM and FUL through in- hibition of autophagy by targeting UCP2. Mill-214 shows potential as a novel therapeutic strategy for overcoming endocrine resistance in ER ＋ breast cancers.

关 键 词：ER + breast cancer ENDOCRINE resistance apoptosis AUTOPHAGY miR-214 UCP2 

分 类 号：R[医药卫生]