Solasodine 是從植物龍葵 (Solanum nigrum) 中所萃取出的固醇類生物鹼。龍葵為茄科茄屬植物，具有鎮咳和抗發炎等功效，其生物鹼含量以未成熟的果實最多。Solasodine 可以用於生產多種固醇類的藥物，並有研究指出能抑制腫瘤細胞增殖。然而，solasodine 對於腫瘤轉移的作用仍不清楚。在本研究中，主要探討在體外模式下，solasodine 對人類肺癌細胞轉移的抑制作用。結果發現 solasodine 抑制肺癌細胞 A549 的存活，並呈劑量依賴性。用非毒性劑量的 solasodine 處理細胞後，透過 Boyden chamber 侵入試驗發現，細胞的侵入能力明顯受到抑制。Solasodine 降低了基質金屬蛋白酶-2/-9 (MMP-2/-9) 和細胞外基質金屬蛋白酶誘導因子 (EMMPRIN) ，同時促進金屬蛋白酶組織抑制蛋白 TIMP-1/-2 及 RECK 基因的 mRNA表現。免疫墨點法檢測顯示，solasodine 能有效的抑制 AKT 磷酸化。此外，solasodine 調降致癌基因 microRNA-21 (miR-21) 的表現，其已知可抑制 RECK 的表達。此研究成果顯示，solasodine 可能是藉由阻斷MMP的表達，抑制 A549 細胞的侵入作用。 Solasodine 也減少 PI3K/AKT 訊息傳遞路徑和調降 miR-21 的表達。這些結果顯示，solasodine 具有抗腫瘤轉移的潛力。 Solasodine is a naturally occurring aglycone of glycoalkaloid in a number of Solanum species (Solanaceae). Solasodine is used for the production of steroid drug in medical industry and that have been reported to inhibit proliferation in various tumor cells. However, the effect of solasodine on tumor metastasis remains unclear. This study investigates the suppression mechanism of solasodine on motility of human lung cancer cell A549 in vitro. Results show that solasodine inhibits viability of lung A549 cells in a dose-dependent manner. When treated with non-toxic doses of solasodine, cells invasion were suppressed significantiy by in vitro Boyden chamber invasion assay. Solasodine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate that solasodine is effective in suppressing Akt phosphorylation. Moreover, solasodine downregulates oncogenic microRNA-21 (miR-21), which has been known to target RECK. Downregulation of miR-21 by miR-21 inhibitor increases RECK expression and decreases cell invasion, suggesting that downregulation of miR-21 by solasodine may contribute to elevate RECK expression and subsequently inhibiting cell invasion. Taken together, the results reveal that inhibition of A549 cell invasion by solasodine may be, at least in part, through blocking MMP expression. Solasodine also reduces PI3K/Akt signaling pathways and downregulates exression of miR-21. These findings demonstrate an attractive therapeutic potential for solasodine in anti-metastatic therapy.
