研究metformin抑制人類肝癌細胞移動和侵襲之機制

二甲雙胍(Metformin)為糖尿病的用藥之一，目前已經有許多利用癌細胞或老鼠作為實驗模式的科學文獻發表，證實Metformin具有抗癌之功效。本研究的目的是在於利用人類肝癌細胞株SK-Hep-1與HA22T/VGH為實驗材料，評估Metformin對肝癌細胞株的移動與侵襲能力，並探討相關細胞內訊號傳遞路徑之影響。研究結果指出，Metformin具有抑制人類肝癌細胞株SK-Hep-1與HA22T/VGH的移動與侵襲的能力。利用gelatin/casein zympgraphy、西方墨點法(western blot)與反轉錄聚合酶鏈鎖反應(reverse transcription-polymerase chain reaction，RT-PCR)來分析Metformin對具有高度侵襲能力的肝癌細胞株SK-Hep-1及HA22T/VGH之影響，結果顯示Metformin明顯地抑制了matrix metalloproteinase-9 (MMP-9) 與 urokinase-type plasminogen activator (uPA)的表現與分泌。除此之外，Metformin抑制了磷酸化ERK1/2與JNK1/2的表現量，以ERK1/2 抑制藥物 PD98059 或JNK1/2抑制藥物SP600125與Metformin來共同處理SK-Hep-1與HA22T/VGH細胞株，發現了這二個細胞株的移動與侵襲的能力會因這些處理方式而顯著的被抑制下來。因此本研究的結論是Metformin具有抑制肝癌細胞株HCC移動與侵襲的潛力，推測將來有機會發展為肝癌的抗癌藥物。

Metformin has been shown to exert anti-cancer activities in several of cancer cells and animal models studies. The purposes of this study were to evaluate the ability of Metformin to inhibit migration and invasion in hepatocellular carcinoma (HCC) cells and to identify the signaling pathways involved in this effect. Our data indicate that Metformin inhibits migration and invasion of SK-Hep-1 and HA22T/VGH human HCC cells. The gelatin/casein zymography, western blot and RT-PCR analysis showed that Metformin significantly inhibited the expression and secretion of matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (uPA) in the highly invasive human SK-Hep-1 and HA22T/VGH cells. Furthermore, Metformin suppressed the expression of phosphorylation levels of ERK1/2 and JNK1/2. Treatment of ERK1/2 inhibitor (PD98059) or JNK1/2 inhibitor (SP600125) enhanced the inhibitory effect of Metformin on migration and invasion of SK-Hep-1 and HA22T/VGH cells. In conclusion, Metformin had potential to suppress the migration and invasion of highly invasive HCC cells and may serve as a potent anti-cancer agent for HCC metastasis.