Nrf2促进肝癌细胞的迁移与侵袭能力

Nrf2 promotes the migration and invasion in hepatocellular carcinoma

目的:探讨核转录因子Nrf2对肝癌细胞迁移及侵袭能力的影响。方法:将Nrf2过表达质粒通过慢病毒包装后分别转染至肝癌细胞系HCC-LM3及Bel-7402中,通过划痕实验、Transwell侵袭实验观察Nrf2对肝癌细胞迁移运动及侵袭能力的影响,使用Western印迹法检测转染后的HCC-LM3及Bel-7402肝癌细胞中基质金属蛋白酶2(MMP2)与基质金属蛋白酶9(MMP9)表达情况,通过收集网络数据库GEPIA中相关临床资料信息分析Nrf2对肝癌患者生存时间的影响。结果:在肝癌细胞系HCC-LM3与Bel-7402中过表达Nrf2,其迁移侵袭能力均明显增强。此外发现过表达Nrf2的HCC-LM3肝癌细胞中MMP2及MMP9表达均增加(t=2.879、5.582,均P<0.05);Bel-7402肝癌细胞转染Nrf2过表达质粒后,其MMP2及MMP9表达也相对增加(t=3.756、2.968,均P<0.05)。高表达Nrf2的肝癌患者生存时间短于低表达Nrf2的肝癌患者(Logrank P=0.042)。结论:肝癌细胞Nrf2高表达可能通过增加MMP2及MMP9的表达,进而促进肝癌细胞迁移及侵袭能力,并且Nrf2高表达与肝癌患者的不良预后有关。

Objective:To study the effect of Nrf2 on the migration and invasion in hepatocellular carcinoma.Methods:HCC-LM3 cells and Bel-7402 cells were transfected with the Nrf2 overexpression plasmid packaged by lentivirus to induce the exogenous expression of Nrf2.The wound healing assay and Transwell migration assay were used to determine the effect of Nrf2 on the invasion and migration in hepatocellular carcinoma.The expression of matrix metalloproteinase 2(MMP2)and matrix metalloproteinase 9(MMP9)was analyzed by Western blot and compared with that in the control.The effect of Nrf2 on the survival time of patients in liver cancer was analyzed through collecting relevant clinic information in GEPIA.Results:After transfection,HCC-LM3 cells and Bel-7402 cells with the Nrf2 overexpression plasmid showed enhanced invasion and migration.In addition,it was found that the expression of MMP2 and MMP9 in HCC-LM3 cells overexpressing Nrf2 were increased(t=2.879,5.582,all P<0.05);meanwhile,the expression of MMP2 and MMP9 in Bel-7402 cells transfected with the Nrf2 overexpression plasmid were also increased(t=3.756,2.968,all P<0.05).The survival time of patients in liver cancer with the high Nrf2 expression was shorter than that of patients with the low Nrf2 expression(Logrank P=0.042).Conclusion:Nrf2 might promote the migration and invasion in hepatocellular carcinoma by increasing MMP2 and MMP9 expression.And the expression of Nrf2 is related to the poor prognosis of patients in liver cancer.