School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072, Australia.
Biochem Biophys Res Commun. 2010 Feb 26;393(1):95-100. doi: 10.1016/j.bbrc.2010.01.087. Epub 2010 Jan 25.
Arylamine N-acetyltransferase 1 is a phase II metabolizing enzyme that has been associated with certain breast cancer subtypes. While it has been linked to breast cancer risk because of its role in the metabolic activation and detoxification of carcinogens, recent studies have suggested it may be important in cell growth and survival. To address the possible importance of NAT1 in breast cancer, we have used a novel small molecule inhibitor (Rhod-o-hp) of the enzyme to examine growth and invasion of the breast adenocarcinoma line MDA-MB-231. The inhibitor significantly reduced cell growth by increasing the percent of cells in G2/M phase of the cell cycle. Rhod-o-hp also reduced the ability of the MDA-MB-231 cells to grow in soft agar. Using an in vitro invasion assay, the inhibitor significantly reduced the invasiveness of the cells. To test whether this effect was due to inhibition of NAT1, the enzyme was knocked down using a lentivirus-based shRNA approach and invasion potential was significantly reduced. Taken together, the results of this study demonstrate that NAT1 activity may be important in breast cancer growth and metastasis. The study suggests that NAT1 is a novel target for breast cancer treatment.
芳香胺 N-乙酰基转移酶 1 是一种 II 相代谢酶，与某些乳腺癌亚型有关。虽然由于其在代谢激活和致癌物解毒中的作用与乳腺癌风险相关，但最近的研究表明它可能在细胞生长和存活中很重要。为了研究 NAT1 在乳腺癌中的可能重要性，我们使用了该酶的新型小分子抑制剂（Rhod-o-hp）来研究乳腺癌腺癌细胞系 MDA-MB-231 的生长和侵袭。该抑制剂通过增加细胞周期 G2/M 期的细胞百分比显著抑制细胞生长。Rhod-o-hp 还降低了 MDA-MB-231 细胞在软琼脂中生长的能力。通过体外侵袭测定，抑制剂显著降低了细胞的侵袭性。为了测试这种作用是否是由于 NAT1 的抑制，使用基于慢病毒的 shRNA 方法敲低了该酶，侵袭潜力显著降低。总之，这项研究的结果表明，NAT1 活性可能在乳腺癌的生长和转移中很重要。该研究表明，NAT1 是乳腺癌治疗的新靶点。
