轉移是造成癌症病人死亡的主要原因，是個多步驟的過程包括細胞吸附和ECM的蛋白降解，來達到細胞的移動。黃連素（berberine）是黃連屬和小蘗屬中的天然成份，具有多種抗發炎和抗癌的生物效果。然而，黃連素抑制癌細胞轉移的機轉至今還不是很清楚。在本試驗中選取子宮頸癌細胞株Si Ha cells，分別處理不同濃度之黃連素觀察其對於癌細胞轉移能力的影響，首先藉由modified Boyden chamber實驗方法，我們發現黃連素對於子宮頸癌細胞株Si Ha cells具有抑制侵襲的能力，由wound healing assay也發現黃連素可以抑制子宮頸癌細胞移動能力。進一步了解黃連素對癌細胞抑制侵襲的機轉，利用Western blot實驗方法，我們發現黃連素會抑制訊息傳遞路徑中FAK及Src磷酸化蛋白的表現，而使得子宮頸癌細胞的侵襲能力下降。由動物試驗證實，於BALB/c裸鼠尾靜脈注射Si Ha cells，發現在有餵食黃連素的組別中，可明顯抑制腫瘤轉移到肺部的能力。由以上結果，黃連素可能是透過抑制FAK pathway中蛋白的磷酸化，調控細胞骨架蛋白進而抑制癌瘤細胞的轉移能力。此外，低濃度的黃連素具有加乘化療藥物(doxorubicin and Taxol)的活性。綜合以上結果，黃連素在未來或許可以應用在預防癌瘤的轉移，或是用於輔助臨床上化療藥物治療子宮頸癌。 Berberine is found in the roots, rhizomes and in the bark of the plant and has several anti-inflammation and anti-cancer biological effects. Nevertheless, limited studies have been available concerning the inhibitory effects of this compound for tumor metastasis. In this research, we treated Si Ha cells with various concentrations of berberine to examine the effect of berberine on factors of cancer metastasis by Boyden invasion assay and wound healing assay. We performed western blot analysis and found that berberine inhibited phosphorylation of FAK and Src and suppress the cell invasion capacities. In vivo anti-tumor study, BALB/c nu/nu nude mice xenograft model were inoculated intravenously with Si Ha cells. The average tumor volume of treatment groups was statistically lower than that of the control group. Berberine was also evidenced by its inhibition on the lung metastasis of Si Ha cells by tail vein injection in vivo. These findings suggested that berberine could reduce the metastasis of cervical cancer cells by inhibited phosphorylation of FAK and regulate the cytoskeleton. Besides, berberine with low concentration enhances the activities of doxorubicin and Taxol. Taken together, berberine may be used for the reduction of the metastasis of cervical cancer cells, thereby constituting an adjuvant treatment for metastasis control.
