蓮蓬萃取物合併順鉑對於抗藥性基因與癌轉移相關因子之研究

蓮蓬(lotus seedpod)是一種傳統的中藥材，而有研究指出其富含多 酚(polyphenol)成份，而具有抗癌活性、抗發炎、抗氧化的作用。順 鉑(cisplatin)是一種治療頭頸部癌(head and neck cancer)常用化療藥物， 但在高劑量使用下會啟動抗藥性基因(Multidrug Resistance Protein, MRP)的表現。而本實驗室先前研究顯示，蓮蓬萃取物(Lotus Seedpod Extracts, LSE)可以增加頭頸部癌以 cisplatin 化療的效果，達到有效抑 制腫瘤生長的效果。因此，本研究擬探討藉由 LSE 合併 cisplatin 的 方式來抑制頭頸部癌 FaDu 細胞之抗藥性基因的表現，以及二者合併 用藥對於癌細胞遷移(migration) 與 上皮- 間 質 轉 化 作 用 (epithelial-mesenchymal transition，EMT)之影響，進而提升抗癌效果。首先利用裸鼠移植腫瘤試驗進行確認，經由西方墨點法分析腫瘤組織 發現，LSE合併cisplatin可以降低cisplatin所誘導的抗藥性基因MRP1、 MRP2 與 MRP5 的表現。過去研究顯示 cisplatin 具有抑制 EMT 的作 用，進一步分析基質金屬蛋白酶(matrix metalloproteinase, MMP)表現 也發現 LSE 合併 cisplatin 組能顯著抑制 MMP-2 與 MMP-9 的蛋白表 現。而 LSE 合併 cisplatin 組也有加成抑制 EMT 中間皮標記蛋白 Vimentin與N-cadherin 之表現情形。另外，對於血管新生(angiogenesis) 相關蛋白 HIF-1α 與 VEGF 的表現於二者合併也有顯著抑制的效果。 最後再利用細胞試驗來確認上述研究，發現 LSE 合併 cisplatin 其抗 藥性基因、EMT 相關蛋白及血管新生相關蛋白皆與動物實驗有一致 的結果。總結，LSE 合併 cisplatin 可抑制抗藥性基因、抑制腫瘤遷移、 EMT 與血管新生作用，未來 LSE 具有開發為輔助癌症治療保健營養 品之潛力。

Lotus seedpod, a traditional Chinese herbal medicine, has shown that it is rich in polyphenols, and has anti-cancer activity, anti-inflammatory and anti-oxidation effects. Cisplatin is a well-known chemotherapeutic drug for the treatment of head and neck cancer, but it also initiates the performance of drug resistance genes at high doses. Previous studies have indicated that can increase combination with cisplatin chemotherapy in head and neck cancer, and achieve the effect of effectively inhibiting tumor growth. Therefore, this study intends to investigate the effect of the combination of LSE and cisplatin. First, in xenograft tumor studies, the tumor tissue was analyzed by Western blotting. It was found that LSE combined with cisplatin can reduce the expression of MRP1, MRP2 and MRP5 induced by cisplatin. Also, epithelial-mesenchymal transition (EMT) can migration and Western blotting of matrix metalloproteinase (MMP) showed that LSE combined with cisplatin group can significantly inhibit the protein levels of MMP-2 and MMP-9. The LSE combined with the cisplatin group also has the additive inhibition of EMT-related markers, Vimentin and N-cadherin. LSE combined with cisplatin significantly inhibited the expressions of angiogenesis-related proteins HIF-1α and VEGF. Finally, using cell experiments to confirm the above studies, it was found the expressions of MRPs, EMT-related proteins and angiogenesis-related proteins, as well as the ability of cell migration, was inhibited by LSE in combination with cisplatin. In summary, LSE combined with cisplatin may inhibit drug-resistance, tumor migration, EMT and angiogenesis, and has the potential to develop health care nutrition products for head and neck cancer treatment in the future.