Diosgenin俗稱薯蕷皂素，是在薯蕷科(Dioscoreaceae)中所萃取出來的天然成分，為植物類固醇皂素 (steroidal sapogenin)之一種，可作為合成固醇類荷爾蒙(steroids)和避孕藥等藥物之原料，並具有降血糖的效果。近年來越來越多的相關研究指出，diosgenin具有抗癌特性，如抑制腫瘤細胞增殖，誘導細胞凋亡等。然而，對於抑制腫瘤轉移方面的影響仍不清楚。在本研究中，主要探討diosgenin是否能夠有效抑制PC-3前列腺癌細胞的侵入能力與移動能力。結果發現，當PC-3細胞以20 μM無毒性劑量處理24小時，細胞爬行和侵入有顯著的被抑制。藉由gelatin zymography與RT-PCR實驗，發現diosgenin可降低matrix metalloproteinase-2 / 9 (MMP-2 / 9)的活性與表現。同時利用西方墨點法，發現diosgenin能夠抑制訊號傳遞蛋白的磷酸化包括PI3K、Akt、ERK、JNK等。經由上述研究結果證實，diosgenin具有抑制PC-3細胞侵入和移動能力，並期望在未來在癌症治療上能夠成為有效的化學治療藥物。 Diosgenin is the primary active ingredient in Dioscorea. Increasing evidences demonstrated that diosgenin had anti-carcinogenic properties, such as inhibiting tumor cells proliferation and inducing apoptosis. However, the effect of diosgenin on tumor metastasis remains unclear. In the present study, we showed that diosgenin inhibited proliferation of prostate cancer cells (PC-3) in a dose-dependent manner. When the cells were treated with non-toxic doses (below 20 μM) of diosgenin, cells migration and invasion were significantly suppressed by wound healing assay and Boyden chamber invasion assay, respectively. Diosgenin also reduced the activity and expression of matrix metalloproteinase-2 and -9 (MMP-2 and -9) which are involved in cell migration and invasion. Meanwhile, diosgenin could significantly suppress the upstream signalings of MMP-2 and -9 including PI3K, Akt, ERK and JNK pathways. Taken together, these results suggested that diosgenin inhibited PC-3 migration and invasion by reducing MMP-2 and -9 activities. These findings reveal a new therapeutic potential for diosgenin on anti-metastatic therapy.
