Chen Xiao-Ping, Liu Shou, Tang Wen-Xin, Chen Zheng-Wang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Technology, Wuhan, 430074, China.
Biochem Biophys Res Commun. 2007 Sep 21;361(2):362-6. doi: 10.1016/j.bbrc.2007.07.033. Epub 2007 Jul 18.
Different cell line with increased thioredoxin-1 (Trx-1) showed a decreased or increased sensitivity to cell killing by cisplatin. Recently, several studies found that the subcellular localization of Trx-1 is closely associated with its functions. In this study, we explored the association of the nuclear Trx-1 with the cisplatin-mediated apoptosis of breast cancer cells MCF-7. Firstly, we found that higher total Trx-1 accompanied by no change of nuclear Trx-1 can not influence apoptosis induced by cisplatin in MCF-7 cells transferred with Trx-1 cDNA. Secondly, higher nuclear Trx-1 accompanied by no change of total Trx-1 can protect cells from apoptosis induced by cisplatin. Thirdly, high nuclear Trx-1 involves in the cisplatin-resistance in cisplatin-resistive cells. Meanwhile, we found that the mRNA level of p53 is closely correlated with the level of nuclear Trx-1. In summary, we concluded that the nuclear Trx-1 is required to resist apoptosis of MCF-7 cells induced by cisplatin, probably through up-regulating the anti-apoptotic gene, p53.
不同的硫氧还蛋白-1（Trx-1）表达增加的细胞系对顺铂诱导的细胞杀伤表现出敏感性降低或增加。最近，多项研究发现Trx-1的亚细胞定位与其功能密切相关。在本研究中，我们探讨了细胞核内的Trx-1与顺铂介导的乳腺癌细胞MCF-7凋亡之间的关联。首先，我们发现总Trx-1水平较高但细胞核Trx-1水平无变化，这并不会影响转染了Trx-1 cDNA的MCF-7细胞中顺铂诱导的凋亡。其次，细胞核Trx-1水平较高但总Trx-1水平无变化，可以保护细胞免受顺铂诱导的凋亡。第三，高细胞核Trx-1水平与顺铂耐药细胞的顺铂耐药性有关。同时，我们发现p53的mRNA水平与细胞核Trx-1水平密切相关。综上所述，我们得出结论，细胞核Trx-1可能通过上调抗凋亡基因p53来抵抗顺铂诱导的MCF-7细胞凋亡。
