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95D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(MMP2,9)的能力,通过Westernblot印迹法,定量分析细胞质内NFκB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,2.5μmol·L-1灵菌红素作用于肿瘤细胞12h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=5μmol·L-1)。灵菌红素可明显抑制肿瘤细胞MMP2,9的分泌,增加肿瘤细胞质内NFκB蛋白量,抑制胞内NFκB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NFκB蛋白活性来抑制MMP2,9的表达,从而抑制癌细胞的浸润转移。
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 EC 50 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.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2004年第10期1091-1095,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
