PS-341对人乳腺癌MDA-MB231细胞uPA、NF-κB表达的影响及其与增殖迁移的关系  

Effect of PS-341 on the expression of NF-κB and uPA as well as cell proliferation and transplant in human MDA-MB231 breast cancer cells

作　　者：薛芳沁[1,2] 杨国华[1,2] 林孟波[1,2] 陈晓耕[1,2] 

机构地区：[1]福建医科大学省立临床医学院 [2]福建省立医院肿瘤外科,福州350001

出　　处：《福建医药杂志》2015年第4期5-8,54,共5页Fujian Medical Journal

基　　金：福建省卫生厅青年科研基金资助项目(2008-1-2)

摘　　要：目的研究硼替佐米(bortezomib,PS-341)对人乳腺癌MDA-MB231细胞真核细胞转录因子-κB(nuclear factor-κB,NF-κB)、尿激酶型血浆纤溶酶原激活因子(uPA)表达的影响及其与增殖迁移的关系。方法 BRDU ELISA法测定细胞增殖活性;Boyden小室培养测定细胞的迁移;Western-blotting测定细胞uPA表达、NF-κB磷酸化水平。结果 1)与对照组(无血清培养基组)相比,血清组(FCS组)呈浓度依赖性促进细胞增殖;当FCS浓度为1%时,细胞增殖明显增加(P<0.05);当FCS浓度为5%时,细胞增殖更为显著(P<0.01)。2)与5%FCS组相比,PS-341呈浓度依赖性抑制细胞增殖活性,PS-341浓度为4ng/mL时细胞增殖活性显著下降(P<0.05)。3)与对照组相比,5%FCS组细胞迁移率明显升高(P<0.05);PS-341呈浓度依赖性抑制5%FCS诱导细胞的迁移,与5%FCS组相比PS-341浓度为4ng/mL时其迁移率显著下降。4)与5%FCS组相比,PS-341为4ng/mL时细胞uPA表达、总NF-κB、核NF-κB水平均明显降低(P<0.05);NF-κB特异性抑制剂PDTC(10μmol/L)能显著降低5%FCS诱导的总NF-κB、核NF-κB水平(P<0.05),但对uPA表达无影响。5)PS-341(4ng/mL)能明显降低5%FCS诱导细胞的增殖与迁移;与PDTC(10μmol/L)相比,两者差异均无统计学意义。结论 PS-341抑制MDA-MB231细胞uPA、NF-κB表达及增殖与迁移;PS-341降低MDA-MB231细胞侵袭力可能与其抑制NF-κB、uPA表达有关。Objective To observe the effect of PS-341 on the expression of NF-kB and uPA as well as cell proliferation and migration in human MDA-MB231 breast cancer cells. Methods Proliferation and migration of human MDA-MB231 cells were respectively determined by Bromodeoxyuridine （BRDU） and Boyden chamber. The expression of uPA and the level of NF- roB-p65 in human MDA-MB231 cells was determined by Western-blotting. Results Compared with the control group （the ser- um-free medium group）, proliferation of human MDA-MB231 cells was increased by 0.2 %-10% FCS in a concentration depend- ent manner, which were significantly elevated by FCS with concentration at 1%FCS. Proliferation of human MDA-MB231 cells was inhibited by PS-341 in a concentration dependent manner, which was significantly decreased by PS-341 4 mg/mL compared with 5%FCS group. Compared with the control group, migration of human MDA-MB231 cell was significantly increased in the 5%FCS group （P〈0.05）, and which was decreased by PS-341 in a concentration dependent manner. Compared with 5%FCS group, migration of human MDA-MB231 cell was greatly decreased by PS-341 with concentration at 4 mg/mL. Compared with 5%FCS group, the expression of uPA, total NF-kB and NF-kB phosphorylation was inhibited by PS-341 （4 mg/mL）. Com- pared with PS-341 group, in PDTC （10μmol/L） group, total NF-kB expression, the level of intranuclear NF-kB, uPA expres- sion, proliferation and migration were not significantly different. Conclusion PS-341 could inhibit the expression of uPA and NF-kB as well as proliferation and migration of human MDA-MB231 cell. The inhibition of PS-341 on proliferation and migra- tion in human MDA-MB231 cell may be related to its inhibition on NF-kB phosphorylation and uPA expression.

关 键 词：硼替佐米 尿激酶型血浆纤溶酶原激活因子 细胞真核细胞转录因子 细胞迁移 细胞增殖 

分 类 号：R737.9[医药卫生—肿瘤]