一种重组蛋白TmSm(T34A)可通过下调细胞周期蛋白D1的表达来抑制乳腺癌干细胞(BCSCs)的增殖并促进其凋亡。

A recombinant protein TmSm(T34A) can inhibit proliferation and proapoptosis to breast cancer stem cells(BCSCs) by down-regulating the expression of Cyclin D1.

作者信息

Ma Xingyuan, Zhang Yi, Kang Yanyan, Li Linfeng, Zheng Wenyun

机构信息

School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Clinical Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.

出版信息

Biomed Pharmacother. 2016 Dec;84:373-381. doi: 10.1016/j.biopha.2016.08.066. Epub 2016 Sep 23.

DOI:10.1016/j.biopha.2016.08.066

PMID:27668537

Abstract

Cancer stem cells (CSCs), a small fraction of cancer cells lines proved with stem cell characteristics, were regarded as "bad seeds" related to recurrence, metastasis and chemotherapy resistance of breast carcinoma in recent years. So inhibiting the growth or inducing the differentiation and apoptosis of CSCs were considered as one of the effective pathways to fight against breast cancer. Based on the recombinant protein TmSm(T34A) that was designed and prepared in our previous experiments for targeting survivin, an inhibitor of apoptosis protein(IAP), in this study, we explored the effects of TmSm(T34A) on BCSCs obtained by enriching in serum-free suspension, sorting and characterizing of MCF-7/ADM. The results showed that TmSm(T34A) could not only inhibit the proliferation and growth of BCSCs by decreasing CD44CD24 proportion and down-regulating the expression of Cyclin D1 significantly, but also induce BCSCs apoptosis evidently. Furthermore, in BCSCs xenograft nude mice administrated TmSm(T34A), the tumor growth was slower than that of the control obviously. Thus it can be seen TmSm(T34A) would be a promising potential protein for treatment of breast cancer by effecting on BCSCs.

摘要

癌症干细胞（CSCs）是一小部分被证明具有干细胞特征的癌细胞系，近年来被视为与乳腺癌复发、转移及化疗耐药相关的“坏种子”。因此，抑制CSCs的生长或诱导其分化及凋亡被认为是对抗乳腺癌的有效途径之一。基于我们前期实验设计制备的靶向凋亡抑制蛋白（IAP）survivin的重组蛋白TmSm（T34A），本研究探讨了TmSm（T34A）对通过无血清悬浮富集、分选及鉴定MCF-7/ADM获得的乳腺癌干细胞（BCSCs）的影响。结果表明，TmSm（T34A）不仅可通过降低CD44CD24比例、显著下调细胞周期蛋白D1表达来抑制BCSCs的增殖与生长，还能明显诱导BCSCs凋亡。此外，在给予TmSm（T34A）的BCSCs异种移植裸鼠中，肿瘤生长明显慢于对照组。由此可见，TmSm（T34A）可能是一种通过作用于BCSCs治疗乳腺癌的有前景的潜在蛋白。