Suppr超能文献

通过下调人乳腺干细胞中八聚体结合蛋白4和Nanog转录因子的表达来降低肿瘤发生能力和耐药性。

Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells.

作者信息

Huang Zheng-Jie, You Jun, Luo Wei-Yuan, Chen Bai-Sheng, Feng Qing-Zhao, Wu Bing-Lin, Jiang Long, Luo Qi

机构信息

Department of Surgical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China.

出版信息

Mol Med Rep. 2015 Mar;11(3):1647-54. doi: 10.3892/mmr.2014.2972. Epub 2014 Nov 18.

Abstract

Breast cancer is the most common type of malignancy among females. Previous studies examining breast cancer tissue have demonstrated the presence of stem cells, and have detected octamer‑binding protein 4 (Oct4) and Nanog transcription factor expression. In the present study, breast cancer stem cells (CSCs) were isolated and enriched from MDA‑MB‑231 breast cancer cell lines, and were defined as MDA‑MB‑231 stem cells using flow cytometry. The expression of Oct4 and Nanog in breast CSCs were detected by quantitative polymerase chain reaction and western blotting. RNA interference (RNAi) was used in order to downregulate the expression of Oct4 and Nanog. Drug resistance and tumor‑initiating capability following in vivo injection of MDA‑MB‑231 stem cells trans-duced with negative RNAi, Oct4 RNAi and Nanog RNAi were compared with that of MDA‑MB‑231 stem cells without siRNA transfection as a control group. In addition the capability of MDA‑MB‑231 breast cancer cells to initiate tumor formation in mice was compared with that of MDA‑MB‑231 stem cells. A paclitaxel inhibition test was also conducted in order to detect resistance of MDA‑MB‑231 breast cancer stem cells to this treatment. The MDA‑MB‑231 stem cells were revealed to exhibit elevated percentages of the cluster of differentiation (CD)44+CD24‑/low subset, high tumorigenicity and resistance to chemotherapy, all of which are characteristic stem cell properties. In addition, the MDA‑MB‑231 stem cells were more tumorigenic in vivo. Furthermore, the breast CSCs also expressed high levels of the Oct4 and Nanog transcription factors. Therefore, downregulation of Oct4 or Nanog expression may reduce chemotherapeutic drug resistance and tumorigenicity in breast CSCs. In conclusion, Oct4 and Nanog expression may be a key factor in the development of resistance to chemotherapy and tumor growth of breast CSCs. This finding indicates that Oct4 or Nanog‑targeted therapy may be a promising means of overcoming resistance to chemotherapy and inhibiting tumor growth in breast cancer treatment.

摘要

乳腺癌是女性中最常见的恶性肿瘤类型。先前对乳腺癌组织的研究已证实存在干细胞,并检测到八聚体结合蛋白4(Oct4)和Nanog转录因子的表达。在本研究中,从MDA-MB-231乳腺癌细胞系中分离并富集了乳腺癌干细胞(CSCs),并使用流式细胞术将其定义为MDA-MB-231干细胞。通过定量聚合酶链反应和蛋白质印迹法检测Oct4和Nanog在乳腺癌CSCs中的表达。使用RNA干扰(RNAi)来下调Oct4和Nanog的表达。将用阴性RNAi、Oct4 RNAi和Nanog RNAi转导的MDA-MB-231干细胞在体内注射后的耐药性和肿瘤起始能力与未进行siRNA转染的MDA-MB-231干细胞作为对照组进行比较。此外,还比较了MDA-MB-231乳腺癌细胞与MDA-MB-231干细胞在小鼠体内引发肿瘤形成的能力。还进行了紫杉醇抑制试验,以检测MDA-MB-231乳腺癌干细胞对该治疗的耐药性。结果显示,MDA-MB-231干细胞表现出较高比例的分化簇(CD)44+CD24-/低亚群、高致瘤性和对化疗的耐药性,所有这些都是干细胞的特征特性。此外,MDA-MB-231干细胞在体内更具致瘤性。此外,乳腺癌CSCs还高水平表达Oct4和Nanog转录因子。因此,下调Oct4或Nanog的表达可能会降低乳腺癌CSCs的化疗耐药性和致瘤性。总之,Oct4和Nanog的表达可能是乳腺癌CSCs化疗耐药性发展和肿瘤生长的关键因素。这一发现表明,针对Oct4或Nanog的治疗可能是克服乳腺癌治疗中化疗耐药性和抑制肿瘤生长的一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be84/4270319/0f09dadf3340/MMR-11-03-1647-g00.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验