Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.
Oncol Rep. 2013 Jul;30(1):125-30. doi: 10.3892/or.2013.2470. Epub 2013 May 15.
Silent mating-type information regulation 2 homologue 1 (SIRT1), a member of the class III histone deacetylase (HDAC) family, is the mammalian ortholog of yeast Sir2. It has been reported to play a key role in a variety of physiological processes such as genomic stability, metabolism, neurogenesis and cell survival. The deacetylase function of SIRT1 has been suggested to play a role in prolonging the life of mammals. However, the suggested functions of SIRT1 as a potential tumor promoter have been challenged by observations of their respective downregulation and upregulation in various types of cancer. Breast cancer patients were included in the present study between 2007 and 2008. Their tumor tissues and paired normal breast tissues were collected and used for evaluation of the expression levels of SIRT1 and Ki67. The effects of SIRT1 on human breast cancer cell lines were also investigated. Immunohistochemistry showed that there is a high correlation between SIRT1 and Ki67 expression. Following treatment with sirtinol (inhibitor of SIRT1), the expression of the pro-survival protein Bcl-2 was markedly decreased in both MCF-7 and MDA-MB-231 cell lines, particularly in MDA-MB-231. Results of the present study revealed that inhibition of SIRT1 activity may be a promising chemotherapeutic strategy against breast cancer.
沉默信息调节因子 2 同源物 1（SIRT1）是组蛋白去乙酰化酶（HDAC）III 类家族的成员，是酵母 Sir2 的哺乳动物同源物。据报道，它在多种生理过程中发挥关键作用，如基因组稳定性、代谢、神经发生和细胞存活。SIRT1 的去乙酰化酶功能被认为在延长哺乳动物寿命方面发挥作用。然而，SIRT1 作为潜在肿瘤促进剂的功能已受到挑战，因为在各种类型的癌症中观察到其表达水平下调和上调。本研究纳入了 2007 年至 2008 年间的乳腺癌患者。收集了他们的肿瘤组织和配对的正常乳腺组织，用于评估 SIRT1 和 Ki67 的表达水平。还研究了 SIRT1 对人乳腺癌细胞系的影响。免疫组织化学显示 SIRT1 与 Ki67 表达之间存在高度相关性。用 sirtinol（SIRT1 抑制剂）处理后，两种 MCF-7 和 MDA-MB-231 细胞系中，特别是在 MDA-MB-231 细胞系中，生存蛋白 Bcl-2 的表达明显下降。本研究结果表明，抑制 SIRT1 活性可能是一种有前途的乳腺癌化疗策略。
