BRMS1在肺癌中的表达及其对肺癌细胞侵袭转移的影响

摘要

目的：探讨乳腺癌转移抑制因子1（BRMS1）在肺癌中的表达及对肺癌细胞侵袭转移能力的影响。方法 Western blot及RT-PCR法检测肺癌及癌旁组织中BRMS1的表达，并将真核表达质粒pCMV-myc-BRMS1及空白质粒转染到肺癌细胞A549。 Transwell法检测细胞迁移和侵袭能力；Western blot 检测核因子-κB（NF-κB）磷酸化水平及下游蛋白基质金属蛋白酶（MMP2），MMP9，骨桥蛋白（Osteopontin），E-钙粘蛋白（E-cadherin）的表达量。结果肺癌组织中BRMS1的蛋白及mRNA表达量都显著低于癌旁组织。与空白质粒组比较，真核表达质粒组中细胞迁移及侵袭能力降低，比值分别为[（0.98±0.10）及（0.17±0.03）]，[（1.29±0.14）及（0.22±0.04）]；NF-κB p65磷酸化水平降低，MMP2，MMP9，Osteopontin表达量下降，E-cadherin表达量上升（P＜0.01）。结论 BRMS1在肺癌组织中低表达，其过表达能显著抑制肺癌细胞A549侵袭转移，推测恢复肺癌组织BRMS1表达可能是转移性肺癌治疗方式之一。%Objective To explore the expression of breast cancer metastasis suppressor 1 ( BRMS1) in lung cancer and its effect on invasion and metastasis of lung cancer cells .Methods The expression of BRMS1 protein and mRNA in lung cancer tissues and normal tissues adjacent to carcinoma was detected by western blot and RT -PCR.PCMV-myc-BRMS1 plasmid and blank plasmid were transfected into A 549.The ability of cell migration and invasion was detected by transwell assay .The phosphorylation of NF-κB and the expression matrix metalloproteinase 2 (MMP2), MMP9, osteopontin and E-cadherin was detected by Western blot .Results The expression of BRMS1 protien [(0.98 ±0.10) and (0.17 ±0.03)] and mRNA [(0.98 ±0.10) and (0.17 ±0.03)] in lung cancer tis-sues was lower than that in normal tissues (P<0.01).Compared with the blank plasmid group , cell migration and invasion ability decreased obviously (P<0.01), the expression of MMP2, MMP9 and osteopontin reduced (P<0.01), the expression of E-cadhetin increased (P<0.01), and the phosphorylation of NF-κB down-regulated in the pCMV-myc-BRMS1 plasmid group.Conclusion The expression of BRMS1 is lower in lung cancer tissues , its over-expression could significantly inhibit the invasion and metastasis of lung cancer A 549 cells.It is speculated that the up-regulated expression of BRMS 1 in lung cancer might be one of the treatment methods for metastatic lung cancer .