灵菌红素抗癌细胞浸润转移作用及对MMPs 活性的影响

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (10): 1091-1095.

灵菌红素抗癌细胞浸润转移作用及对MMPs 活性的影响

张靖, 沈亚领, 刘建文

华东理工大学生物反应器工程国家重点实验室, 新药药理研究室, 上海200237

收稿日期:2004-07-31 修回日期:2004-09-09 出版日期:2004-10-26 发布日期:2020-11-23
通讯作者: 刘建文, 男, 博士, 教授, 博士生导师, 主要从事肿瘤药理学及生物活性物质的功效研究。Tel:021-64252044 E-mail:liujian @ecust.edu.cn
作者简介:张靖, 女, 硕士研究生, 研究方向为肿瘤药理学。Tel:021-64253871 E-mail:biostudent@163. com

Inhibition of prodigiosin on migration and invasion of cancer cells and expression of MMPs

ZHANG Jing, SHEN Ya-Ling, LIU Jian-Wen

Research Laboratory of New Drug Pharmacology, State Key Laboratory of Bioreactor Engineer, East China University of Science and Technology, Shanghai 200237, China

Received:2004-07-31 Revised:2004-09-09 Online:2004-10-26 Published:2020-11-23

摘要/Abstract

摘要： 目的: 研究灵菌红素在体外对癌细胞浸润、转移的抑制作用, 并探讨其分子机理。方法: 用创伤试验测定高转移性人肺腺癌细胞95-D 的运动能力, 用浸润杯试验法研究细胞的浸润能力, 用明胶酶谱分析法观察细胞分泌基质金属蛋白酶2 和9(MMP-2,-9) 的能力, 通过Western-blot 印迹法, 定量分析细胞质内NF-κB 的蛋白量, 用高效液相色谱(HPLC) 检测细胞内的药物浓度。结果: 在非细胞毒作用的浓度范围, 2. 5 μmol·L^-1 灵菌红素作用于肿瘤细胞12 h后, 抑制癌细胞的运动能力达42 %, 同时, 显著抑制癌细胞的浸润转移(EC₅₀=5 μmol·L^-1) 。灵菌红素可明显抑制肿瘤细胞MMP-2, 9 的分泌, 增加肿瘤细胞质内NF-κB 蛋白量, 抑制胞内NF-κB 蛋白的活化。灵菌红素能有效通过细胞膜, 其药效学作用与细胞内药物浓度相关。结论: 灵菌红素能有效地进入细胞内, 通过调节肿瘤细胞内NF-κB 蛋白活性来抑制MMP-2,-9 的表达, 从而抑制癌细胞的浸润转移。

关键词: 癌转移, 浸润, MMP-2,-9, NF-κB, 灵菌红素

Abstract: AIM: To observe the inhibition and mechanisms of prodigiosin on migration and invasion of cancer cells in vitro.METHODS: The migration and invasion of cells was measured by wound healing assay and the transwell assay. The expression of MMP-2,-9 was analyzed by gel zymography assay. The expression of NF-κB protein in cytoplasm was measured by western-blot. The concentration of prodigiosin in 95-D cells was analyzed by HPLC.RESULTS: The inhibitive effects on migration of the cells reached 42 %when cells were treated with 2. 5 μmol·L^-1 prodigiosin for 12 h and under the concentration of no cytotoxicity actions. The invasion of 95-D cells was dose-dependently inhibited by prodigiosin with EC50 of 5 μmol·L^-1.In addition, prodigiosin effectively inhibited the activity of MMP-2,-9. Prodigiosin also elevated the protein level of NF-κB in cytoplasm and then inhibited the activity of NF-κB. The results of HPLC showed that prodigiosin effectively entered cells, and the pharmacological effect of prodigiosin was dependent on the drug concentration in cells.CONCLUSION: Prodigiosin can effectively enter cells and inhibit the expression of MMP-2,-9 through the inhibition of the activity of the NF-κB, thereby it can inhibit the invasion and metastasis of tumor cells.

Key words: invasion, metastasis, MMP-2,-9, NF-κB, prodigiosin

中图分类号:

R979.1
R966

张靖, 沈亚领, 刘建文. 灵菌红素抗癌细胞浸润转移作用及对MMPs 活性的影响[J]. 中国临床药理学与治疗学, 2004, 9(10): 1091-1095.

ZHANG Jing, SHEN Ya-Ling, LIU Jian-Wen. Inhibition of prodigiosin on migration and invasion of cancer cells and expression of MMPs[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(10): 1091-1095.

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