补骨脂素对乳腺癌MCF-7和MDA-MB-231细胞体外作用的比较研究

Comparative Study on the Antitumor Effects of Psoralen on Human Breast Cancer Cell Line MCF-7 and MDA-MB-231 in Vitro

【目的】观察并比较补骨脂素对人乳腺癌MCF-7和MDA-MB-231细胞的抑制作用。【方法】以不同浓度的补骨脂素(25.000、12.500、6.250、3.125μg/mL)对人乳腺癌细胞株MCF-7[雌激素受体(ER)阳性]和MDA-MB-231(ER阴性)进行体外抑制实验,运用流式细胞仪观察细胞的周期变化,Annexin V和碘化丙锭(PI)双染法观察细胞凋亡情况,基因芯片检测补骨脂素对两种人乳腺癌细胞基因表达谱的影响。【结果】补骨脂素对人乳腺癌细胞株MCF-7有显著抑制作用(P<0.05),半数抑制浓度(IC50)为15.160μg/mL;作用24 h后,S期细胞明显减少,G1、G2期细胞增加,早期凋亡细胞明显增多。而补骨脂素对MDA-MB-231细胞无明显抑制作用,仅早期凋亡细胞增多。人类全基因组寡核苷酸微阵列芯片杂交结果显示,补骨脂素可以使MCF-7细胞出现1 053个差异表达基因,其中表达上调的有456个,表达下调的有657个。【结论】补骨脂素对ER阳性的乳腺癌MCF-7细胞具有一定的抑制作用,其抑制肿瘤细胞生长的机理可能与将肿瘤细胞阻止在G2期相关。

Objective To compare the antitumor effects of psoralen on human breast cancer cell line MCF-7 and MDA-MB-231. Methods In-vitro inhibitory effects of various concentrations of psoralen （25, 12.5, 6. 25 and 3. 125 μg/mL respectively） on MCF-7 cells with estrogen-receptor （ER） postive and on MDA-MB-231 cells with ER negative were carried out. Cell cycle was observed with flow cytometry （FCM）, and cell apoptosis was examined by Annexin V-propidium iodide （PI） staining. Gene chip was used for the examination of changes of gene expression pattem. Results Psoralen inhibited the growth of MCF-7 cells in a dose-dependent manner, with IC50 being 15. 160 μg/mL; FCM assay showed the percentage of G1- and G2- phase cells increased while that of S-phase cells decreased, and cell apoptosis was obviously increased at early stage. Psoralen had no inhibitory effect on the growth of MDA-MB-231 cells, but cell apoptosis was increased at early stage. There were 1053 genes with differential expression in MCF-7 cells assessed by cDNA chips. Of the expression of 1053 genes, the expression of 657 genes was down-regulated and that of 456 gene was up-regulated. Conclusion Psoralen has certain inhibitory effect on the proliferation of ER-positive MCF-7 cells, and its inhibitory mechanism on the growth of breast cancer is probably related with the arrest of the cell at G2 phase by the drug.