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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。
Objective To investigate the role of HERG K+ channels in the invasion and migration of hepatoma cells induced by VEGF. Methods The expression of HERG K+ channels in the normal liver cell line L-02 and hepatoma cell line SMMC-7721 was detected by patch clamp technique. The effect of HERG K+ channel inhibitor E-4031 was detected by the Bodyen-Chamber system. The effect of VEGF on the invasiveness and migration potential of SMMC-7721 cells was detected by ELISA. The changes of VEGF levels in the culture supernatant after E-4031 treatment of SMMC-7721 cells were detected by ELISA. Results HERG K+ channels were expressed in SMMC-7721 cells but not in L-02 cells; and VEGP-induced SMMC-7721 cell invasion and migration were inhibited in a dose-dependent manner by E-4031; HERG was blocked. The level of VEGF in the supernatant after the K+ channel was significantly reduced. Conclusion HERG K+ channels exist in hepatoma cells, which can affect the invasion and migration of hepatoma cells by regulating the secretion of VEGF. Thus, the HERG K+ channel may become a new marker for diagnosing liver cancer and judging the prognosis and a new target for treatment.