全反式维甲酸抑制Ets-1介导的肝癌7402细胞离散和侵袭及其分子机制

Inhibitory effect and its molecular mechanism of all-tans retinoic acid on hepatoma 7402 cell's scatter and invasion induced by transcription factor Ets-1

目的 研究全反式维甲酸(ATRA)对Ets介导的实体瘤细胞侵袭转移性的影响及探讨其分子机制,寻找新的抗癌药物作用靶点。方法 采用基因转染的方法,将Ets-1基因高表达在低侵袭转移的肝癌7402细胞中,使其增殖、离散侵袭能力增强,再经ATRA处理细胞,用细胞生物学方法检测细胞增殖性、肝癌细胞离散性及穿透Transwell聚碳酯膜能力的改变。并用Northern杂交、Western印迹等分子生物学手段检测ATRA的分子作用机制。结果 发现ATRA可抑制7402细胞因Ets-1高表达而增强的增殖、离散、侵袭性,可下调Ets、c-Met基因的表达,使MAPK、PI3K信号途径中两个关键分子 Erk/Akt的磷酸化水平降低。结论ATRA可能通过下调Ets基因的表达,进而使c-Met表达水平降低,导致MAPK、PI3K信号转导减弱而抑制肿瘤细胞增殖和侵袭;Ets基因可以作为抗癌药物作用的靶点来筛选药物或进行药理研究。

ABSTRACT AIM To study the effect and its molecular mechanism of All-trans Retinoic Acid (ATRA) on tumor invasion and to find a new target of anti-tumor drug. METHODS A high proliferation, scatter, and invasion Hepatoma 7402 cell line with high Ets-1 experssion was set up by transgenic method. Then to study the biological changes on the transgenic cell line treated with ATRA or without using cellar biological methods. Using molecular methods such as northern blot and western blot etc, to study its molecular mechanism. RESULTS An inhibitory effect of ATRA on the proliferation and invasion of the Hepatoma 7402 cell was found. ATRA were also found to down-regulate the expression of Ets and c-Met in the 7402-cell line. The phosphorylation of Erk and Akt were decreased in the cells treated with AT-RA. CONCLUSION ATRA may inhibit the 7402 cell growth and metastasis through down-regulation the expression of Ets and c-Met, then block the MAPK and PI3K signal pathway. Ets may be a target of anti-tumor drug.