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丁酸钠(Sodium butyrate,NaB)是一种组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitors,HDACi),通过增加组蛋白的乙酰化,使染色质处于开放状态,便于基因转录与表达。多梳基因家族(Polycomb group genes,PcG)的成员Bmi-1蛋白可以对染色体组蛋白进行修饰,使一些抑癌基因如p14、P16和P21基因等表达沉默,同时Bmi-1蛋白通过Wnt信号通路激活原癌基因c-Myc,使Bmi-1、Wnt信号通路、c-Myc组成一个正反馈循环,还可以上调端粒酶的表达,导致肿瘤的发生。HDACi可以下调Bmi-1蛋白的表达,并通过上调p14、p16和p2l等的表达以及线粒体通路和Wnt信号通路抑制肿瘤细胞的增殖、分化,诱导肿瘤细胞凋亡。HDACi将可能为肿瘤的治疗提供一个广阔的前景,本研究将对Bmi-1在丁酸钠诱导肿瘤细胞凋亡过程中的作用机制作一综述。
Sodium butyrate (NaB), a histone deacetylase inhibitors (HDACi), facilitates the transcription and expression of genes by increasing histone acetylation, allowing chromatin to be released. Bmi-1, a member of Polycomb group genes (PcG), can modify the chromosomal histone to silence the expression of some tumor suppressor genes such as p14, P16 and P21 genes. Meanwhile, Bmi-1 protein is transduced through the Wnt signaling pathway Activation of the proto-oncogene c-Myc, Bmi-1, Wnt signaling pathway, c-Myc constitute a positive feedback loop, but also up-regulate the expression of telomerase, leading to tumorigenesis. HDACi can down-regulate the expression of Bmi-1 protein and inhibit the proliferation and differentiation of tumor cells by up-regulating the expression of p14, p16 and p21, mitochondrial pathway and Wnt signaling pathway, and inducing tumor cell apoptosis. HDACi may provide a promising prospect for the treatment of cancer. This review will summarize the mechanism of Bmi-1 in the sodium butyrate-induced apoptosis of tumor cells.