紅麴山藥酒精萃取物對於大腸癌細胞 生長及轉移治療效果之研究

Abstract

紅麴發酵產物在亞洲應用於膳食已經有千年以上歷史。本研究以人類和小鼠大腸癌細胞株評估紅麴山藥酒精萃取物對大腸癌細胞之細胞增生、細胞轉移及細胞週期之影響。紅麴山藥酒萃物對大腸癌細胞HCT116、HT29、SW480、SW620與CT26皆有顯著的毒殺能力，對於CT26及SW480更可抑制其轉移作用，並透過抑制細胞週期停滯於sub-G1 phase，誘發大腸癌細胞走向細胞凋亡。此外，本研究利用誘導BALB/c小鼠產生腫瘤，分別建立全身性和局部性大腸癌動物模式，評估紅麴山藥對於大腸癌治療之功效。在局部性動物模式中，首先在小鼠後腿以皮下注射方式植入大腸癌細胞CT26，當腫瘤生長至150 ± 10 mm3 後，每天餵食不同濃度的紅麴山藥，並於四週後犧牲動物。全身性動物模式中，以脾臟注射的方式植入小鼠大腸癌細胞CT26，模擬臨床上大腸癌發生肝臟轉移的症狀，並於隔天摘除脾臟，同時開始每天餵食不同濃度紅麴山藥，持續四週，並分別在一到四週犧牲動物。研究結果顯示，不論是局部性或全身性之大腸癌動物模式，餵食紅麴山藥的實驗組其腫瘤嚴重程度都較控制組來的低，不但抑制腫瘤生長，更有抑制癌細胞轉移至其他器官的能力。因此，在大腸癌治療過程中，紅麴山藥具有相當潛力可以應用為一輔助治療劑。

Red mold fermented products have been applied to food for over centuries in Asia. In the present study, ethanol extract of red mold dioscorea (RMDE) was selected for investigating the effects on cell proliferation, cell migration and cell cycle in human and mouse colon cancer cells. The results showed that RMDE decreased cellular proliferation in HCT116, HT29, SW480, SW620 human colon cancer cells and CT26 mouse colon cancer cells. RMDE also decreased cellular migration in CT26 and SW480. RMDE inhibited cell cycle arrest at sub-G1 phase with further apoptosis induced. In the animal model, in order to evaluate the effect of RMDE on colon cancer, we established local and systemic colon cancer model in BALB/c by injecting CT26 mouse colon cancer cells. In local model, CT26 were injected subcutaneously. When tumor size reached 150 ± 10 mm3, mice were gavaged with different dose of RMDE daily and sacrificed after 4 weeks. In systemic model, intrasplenic injection of CT26 was performed to simulate the clinical liver metastasis of colon cancer. Different dose of RMDE daily gavage began at the next day for 4 weeks and mouse were sacrificed in 1, 2, 3, 4 weeks, respectively. Regardless of local or systemic model, the results showed that the tumor size and degree were reduced by RMDE. Cell proliferation and migration were inhibited by RMDE, indicating the potential of red mold dioscorea in cure treatment or adjuvant for colon cancer therapy.