HERG K^＋通道对VEGF诱导的肝癌细胞迁移和侵袭的影响

目的研究HERG K＋通道对VEGF诱导的肝癌细胞在侵袭和迁移方面的调节作用。方法运用膜片钳技术分别检测正常肝细胞系L-02和肝癌细胞系SMMC-7721中HERG K＋通道的表达情况;采用Bodyen-Chamber系统检测在HERG K＋通道特异性抑制剂E-4031作用后,对VEGF诱导的SMMC-7721细胞侵袭力和迁移潜能方面的影响;ELISA法检测E-4031处理SMMC-7721细胞后,培养基上清中的VEGF水平的变化。结果 HERG K＋通道在SMMC-7721细胞中表达,而在L-02细胞中不表达;且VEGP诱导的SMMC-7721细胞侵袭和迁移现象可被E-4031呈剂量依赖性地抑制;在阻断HERG K＋通道后上清中VEGF水平明显降低。结论肝癌细胞中存在HERG K＋通道,它可通过调控VEGF分泌水平来影响肝癌细胞的侵袭和迁移能力。由此,HERG K＋通道将有可能成为诊断肝癌和判断预后的新标志物及治疗的新靶位。

Effect of HERG K + Channels on the Invasion and Migration of Hepatocarcinoma Cells Induced by VEGF

Objective To study the effect of HRRG K＋ channels on the invasion and migration of hepatocarcinoma（HCC） cells induced by vascular endothelial gtowth factor（VEGF）.Methods The current of HRRG K＋ channels in HCC line SMMC-7721 and normal liver cell line L-02 were recorded by parch camp technique.Bodyen-Chamber assays was used to monitor the VEGF-indaced invasion and migration of SMMC-7721 cells after treatment with HERG K＋ channels specific inhibitor E-4031.The secretion levels of VEGF in the supematant of SMMC-7721 cells treated with E-4031 were measured by ELlSA assay.Results We recorded HERG K＋current in SMMC-7721,but not in L-02 cell.In addition,we demonstrated the invasion and migration of VEGF-induced HCC cells could be dose dependently inhibited by E-4031,and the VEGF levels secreted by HCC cells were obviously decreased after HERG K＋ channels blocked by E-4031.Conclusion HERG K＋ current exists in the HCC cells,not in normal liver cells.Moreover,HERG K＋ channels can influence the invasion and migration of HCC cells through regulating the secretion of VEGF.Therefore,the potential implications of HERG K＋ channels as a new biomarker for diagnosis and prognosis of carcinogenesis,and a new pharmacological targer for liver cancer therapy are attracting increasing interest.