發明
中華民國
107109554
I 661831
使用台灣白鳳菜之經水萃取的產物來治療肝細胞癌以及抑制肝細胞癌幹細胞的生長
高雄醫學大學
2019/06/11
肝癌是全世界第六常見的癌症。然而,目前治療的效果仍然有限,因此,找尋具有新穎性療效之藥物是當務之急的。在台灣民間中草藥中,和白鳳菜[Gynura divaricata (L.) DC. ssp. formosana]被用來治療高血糖及肝炎方面疾病,但並沒有針對肝癌的預防或治療上的應用。我們發現白鳳菜水萃取物對於肝癌細胞株有劑量依存關係的毒殺性,並可以增強cisplatin, 5-Fluorouracil、doxorubicin之化學治療的效果。重要的是,白鳳菜水萃取物相較於cisplatin更能有效抑制肝癌癌幹細胞球體的生長。動物實驗發現,白鳳菜水萃取物能夠明顯抑制肝癌異種移植腫瘤的生長,且能夠增強cisplatin的治療效果,延長腫瘤復發時間。我們也發現白鳳菜水萃取物可以藉由抑制Wnt pathway來阻止肝癌幹細胞生長。此外,白鳳菜水萃取物也能夠改善因為cisplatin所造成的體重下重。因此,其潛藏之治療效果能成為肝癌病患治療上的食物補充品。 Liver cancer is the sixth common cancer and the second leading cause of cancer death worldwide. Despite the available treatment options, liver cancer remains the second leading cause of cancer death globally and the treatment outcome for patients have not been satisfactory. Gynura divaricata (L.) DC. ssp. formosana is widely used folk herbal medicine for treating diabetes and hepatitis. The anti-liver cancer effect of water extract of the aerial part of G. divaricata (GD extract) was evaluated. A moderate cytotoxicity of GD extract in liver cancer cells was observed. GD extract sensitized Huh7 cells to cisplatin and 5-fluorouracil. Interestingly, GD extract inhibited cancer sphere formation and reduced the expression of cancer stem cell (CSC) markers. Importantly, GD extract suppressed Huh7 tumor growth and prolong the anti-liver cancer effect of cisplatin in vivo. Treatment of GD extract resulted in reductions of Wnt reporter activity and the expression of Wnt target genes. Moreover, suppression of β-catenin were observed in both GD extract treated Huh7 spheres and xenograft tumors. Surprisingly, the body weight loss was recovered faster in the cis and GD extract combination group than cis only group. Accordingly, our findings suggested that G. divaricata could target liver CSC via suppressing Wnt pathway and be a functional food with therapeutic benefit for HCC patients.
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