[1]周游,王雅楠,张堃,等.ER阳性乳腺癌中西达本胺逆转内分泌耐药[J].深圳大学学报理工版,2018,35(4):339-344.[doi:10.3724/SP.J.1249.2018.04339]
 ZHOU You,WANG Yanan,ZHANG Kun,et al.Chidamide reverses endocrine resistance in estrogen receptor-positive breast cancer[J].Journal of Shenzhen University Science and Engineering,2018,35(4):339-344.[doi:10.3724/SP.J.1249.2018.04339]
点击复制

ER阳性乳腺癌中西达本胺逆转内分泌耐药()
分享到:

《深圳大学学报理工版》[ISSN:1000-2618/CN:44-1401/N]

卷:
第35卷
期数:
2018年第4期
页码:
339-344
栏目:
生物工程
出版日期:
2018-07-10

文章信息/Info

Title:
Chidamide reverses endocrine resistance in estrogen receptor-positive breast cancer
作者:
周游王雅楠张堃朱静忠宁志强
深圳微芯生物科技股份有限公司,广东深圳 518057
Author(s):
ZHOU You WANG Yanan ZHANG Kun ZHU Jingzhong and NING Zhiqiang
Shenzhen Chipscreen Biosciences Ltd., Shenzhen 518057, Guangdong Province, P.R.China
关键词:
药理学乳腺癌西达本胺内分泌治疗他莫昔芬氟维司群表皮生长因子
Keywords:
pharmacology breast cancer chidamide endocrine therapy tamoxifen fulvestrant epidermal growth factor
分类号:
R 730
DOI:
10.3724/SP.J.1249.2018.04339
文献标志码:
A
摘要:
内分泌治疗是雌激素受体阳性乳腺癌的主要治疗手段,但耐药的发生限制了其应用,本研究试验证组蛋白去乙酰化酶抑制剂西达本胺是否可用于逆转雌激素受体阳性乳腺癌内分泌耐药.通过MTS细胞增殖检测实验发现,4-羟他莫西芬与西达本胺单药均对雌激素受体阳性乳腺癌细胞MCF-7的增殖具有一定抑制作用,且在两药联合时表现为药效叠加.表皮生长因子可诱导MCF-7对4-羟他莫西芬的耐药,而西达本胺可逆转这种耐药.通过Western Blot实验发现西达本胺可抑制表皮生长因子引起的MEK、ERK、AKT等激酶的磷酸化,并可抑制雌激素受体的磷酸化.原位移植瘤动物模型的体内药效实验也显示药物联用组比单药组更强的抑瘤作用.上述研究结果表明西达本胺在雌激素受体阳性乳腺癌细胞中具有逆转内分泌耐药的作用,作用机制可能与其对表皮生长因子下游通路及雌激素受体活化通路的抑制有关.
Abstract:
Endocrine therapy is the mainstay of treatment for estrogen receptor-positive breast cancer, but the occurrence of drug resistance limits its application. The aim of this study is to explore if chidamide, a histone deacetylase inhibitor, can be used for reversing endocrine resistance in estrogen receptor-positive breast cancer. MTS cell proliferation assay shows that monotherapy with 4-hydroxytamoxifen and chidamide have certain inhibitory effects on the proliferation of MCF-7 (estrogen receptor-positive breast cancer cell line), and additive effects upon combination. Epidermal growth factor induces resistance of MCF-7 to 4- hydroxytamoxifen, while chidamide can reverse this resistance. Western blot experiment shows that epidermal growth factor-induced phosphorylation of MEK, ERK, AKT can be reduced by chidamide, as well as the phosphorylation of estrogen receptor. In vivo efficacy in orthotopic transplantation breast tumor models also indicate that the effect of combination of chidamide and fulvestrant is more visible compared with monotherapy. These findings suggest that chidamide can reverse epidermal growth factor induced endocrine resistance in estrogen receptor positive breast cancer cells, and this reverse effect may be related with its inhibition of the pathways downstream of the epidermal growth factor and the pathway of activation of estrogen receptor.

相似文献/References:

[1]黎丽,李玉珍,丁利平,等.角蒿咖啡酸酯对小鼠耳肿胀的抑制作用[J].深圳大学学报理工版,2017,34(1):46.[doi:10.3724/SP.J.1249.2017.01046]
 Li Li,Li Yuzhen,et al.Effect of Incarvillea caffeate on mouse ear edema[J].Journal of Shenzhen University Science and Engineering,2017,34(4):46.[doi:10.3724/SP.J.1249.2017.01046]

更新日期/Last Update: 2018-06-20