乌司他丁对乳腺癌细胞迁移、黏附、侵袭能力的影响及机制

Effect of ulinastatin on adhesion,invasion and migration of human breast cancer cell and its mechanism

目的探讨乌司他丁(UTI)对乳腺癌MDA-MB-231雌激素受体阴性(ER-)和MCF-7ER阳性(ER+)细胞迁移、黏附、侵袭的影响及机制。方法体外培养MDA-MB-231和MCF-7细胞,并分别将其随机分为5组:空白组,UTI高、中、低剂量组,UTI+多西紫杉醇(TXT)组。ELISA检测两种细胞培养液中中性粒细胞弹性蛋白酶(NE)水平,Western blot检测两种细胞蛋白激酶B(Akt)、整合素β1(Integrinβ1)的表达;改良MTT实验、Transwell小室实验观察两种细胞的黏附、迁移和侵袭。结果 UTI干预后,ER-/+乳腺癌细胞的迁移、黏附、侵袭均降低;两种乳腺癌细胞培养液中NE的水平和细胞Akt及Integrinβ1的表达均明显下降。结论 UTI抑制乳腺癌细胞的迁移、黏附、侵袭,可能与其降低乳腺癌细胞NE、Akt及Integrinβ1的表达有关。

Objective To study the effect of ulinastatin（UTI） on adhesion,invasion and migration of estrin receptor-negative（ER-） breast cancer cell MDA-MB-231 and estrin receptor-positive（ER＋） MCF-7 and its relevant mechanism.Methods The breast cancer cell line MDA-MB-231 and MCF-7 were randomly divided into 5 groups respectively：control,UTI at low,medium and high doses,TXT＋UTI groups.The neutrophil elastase（NE） in both two kinds of cell culture supernates was detected by ELISA.Western blot was used to quantify the proteins of protein kinase B（Akt） and integrinβ1 of MDA-MB-231and MCF-7.The adhesion ability of the two kinds of cells was tested by MTT assay with Matrigel.The invasion ability of cells was tested by Transwell chamber with Matrigel.The migration of cells was examined by Transwell chamber.Results The expression of Akt and integrinβ1 in MDA-MB-231 and MCF-7 was decreased compared with the control group,while also decreased the NE levels of cell culture supernates.The transfer of MDA-MB-231 and MCF-7 cells was inhibited compared with the control group,but TXT ＋ UTI was superior to UTI.Conclusion UTI can inhibit the transfer of the MDA-MB-231 and MCF-7 cells by down regulation of the Akt,integrinβ1 and NE.