乌斯他丁和环磷酰胺对乳腺癌细胞增殖和侵袭及MMP-9表达的影响

目的观察乌斯他丁(UTI)和环磷酰胺(CTX)对体外培养的乳腺癌细胞MCF-7(雌激素受体阳性)和乳腺癌细胞MDA-MB-231(雌激素受体阴性)增殖、侵袭及基质金属蛋白酶-9(MMP-9)表达的影响。方法将体外培养的乳腺癌细胞MCF-7和MDA-MB-231分别分为8组:对照组、UTI高、中、低剂量组、CTX组、CTX+UTI高、中、低剂量组,分别用相应药物处理。采用MTT法检测细胞的增殖能力;流式细胞仪分析细胞周期;RT-PCR检测细胞MMP-9基因的表达;Boyden小室侵袭试验检测两种细胞的浸袭能力。结果UTI可明显抑制MCF-7和MDA-MB-231细胞的增殖,使细胞周期阻滞在G2/M期,并能使2株细胞中MMP-9基因的转录水平下降,细胞的增殖侵袭能力降低。CTX与UTI联合应用,其作用效果优于CTX单独使用。结论UTI能增强CTX诱导的乳腺癌细胞MCF-7和MDA-MB-231的增殖抑制作用,二者具有协同效应。其机制可能与UTI降低细胞MMP-9基因的表达等有关。

Effects of Ulinastatin and Cyclophosphamide on Proliferation and Invasion of Breast Cancer Cells and Expression of Matrix Metalloproteinase-9

Objective To observe the effects of ulinastatin(UTI)and cyclophosphamide(CTX)on the proliferation and invasion of estrin receptor-positive(ER+)breast cancer MCF-7 cells and estrin receptor-negative(ER-)breast cancer MDA-MB-23 cells, cultured in vitro, as well as expression of matrix metalloproteinase-9 (MMP-9). Methods The MCF-7 and MDA-MB-231 cells cultured in vitro were divided into one control and seven test groups respectively. The cells in control group were untreated, and those in seven test groups were treated with UTI at high, moderate and low dosages, CTX and CTX + UTI at high, moderate and low dosages respectively. The proliferation of cells was determined by MTT method, the cell cycle by flow cytometry, and the expression of MMP-9 by RT-PCR. The invasion abilities of MCF-7 and MDA-MB-23 cells were determined by Boyden chamber assay. Results UTI inhibited the proliferations of MCF-7 and MDA-MB-231 cells significantly, blocked the cell cycle at G2 / M stage, decreased the expression levels of MMP-9 and the invasion abilities of the cells. However, the effect of combined treatment with CTX and UTI was superior to that with CTX alone. Conclusion UTI enhanced the inhibitory effect on proliferations of breast cancer MCF-7 and MDA-MB-231 cells induced by CTX. Meanwhile, UTI showed synergistic effect with CTX by a potential mechanism of decreasing the expression of MMP-9.