N-乙酰半胱氨酸对T24人膀胱癌细胞侵袭及MMP-9产生的抑制作用
Inhibitory effect of N-acetylcysteine on invasion and MMP-9 production of T24 human bladder cancer cells.
作者信息
Kawakami S, Kageyama Y, Fujii Y, Kihara K, Oshima H
机构信息
Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan.
出版信息
Anticancer Res. 2001 Jan-Feb;21(1A):213-9.
BACKGROUND
MMPs play a crucial role in the process of cancer invasion and metastasis.
METHODS
The influence of NAC on invasion and MMP-9 production of human bladder cancer cell line T24 was investigated using an in vitro invasion assay, gelatin zymography, Western and Northern blot analyses and RT-PCR assays.
RESULTS
TPA increased the number of invading T24 cells through reconstituted basement membrane more than 10-fold compared to basal condition. NAC inhibited TPA-enhanced invasion dose-dependently. TPA increased the MMP-9 production by T24 cells without altering expression of TIMP-1 gene, while NAC suppressed TPA-enhanced production of MMP-9. Neither TPA nor NAC altered TIMP-1 mRNA level in T24 cells. In vitro experiments demonstrated that MMP-9 was directly inhibited by NAC but was not influenced by TPA.
CONCLUSION
NAC limits invasion of T24 human bladder cancer cells by inhibiting the MMP-9 production in addition to a direct inhibition of MMP-9 activity.
背景
基质金属蛋白酶（MMPs）在癌症侵袭和转移过程中起关键作用。
方法
采用体外侵袭试验、明胶酶谱法、蛋白质免疫印迹和Northern印迹分析以及逆转录-聚合酶链反应（RT-PCR）试验，研究了N-乙酰半胱氨酸（NAC）对人膀胱癌细胞系T24侵袭及MMP-9产生的影响。
结果
与基础状态相比，佛波酯（TPA）使穿过重组基底膜的T24侵袭细胞数量增加了10倍以上。NAC剂量依赖性地抑制TPA增强的侵袭。TPA增加了T24细胞MMP-9的产生，而不改变金属蛋白酶组织抑制因子-1（TIMP-1）基因的表达，而NAC抑制TPA增强的MMP-9产生。TPA和NAC均未改变T24细胞中TIMP-1 mRNA水平。体外实验表明，NAC直接抑制MMP-9，但不受TPA影响。
结论
NAC除直接抑制MMP-9活性外，还通过抑制MMP-9的产生来限制T24人膀胱癌细胞的侵袭。
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