5-Fluorouracil (5-FU) 是治療結腸直腸癌最常使用之化學治療藥物，但使用 5-FU 常產生許多副作用。利用植化素聯合化學藥物治療癌症，可能可以減少副作用及提高患者存活率。海巴戟天 (Morinda citrifolia)，又名諾麗，證明具有抗氧化能力，及誘導腫瘤細胞凋亡。本研究探討海巴戟天葉乙醇萃取物上清液 (LES) 及其分劃物 F1 與 F3 (芸香苷) 聯合 5-FU，對結腸直腸癌 HT-29 細胞存活率、氧化壓力及細胞內訊息傳遞作用之影響。結果顯示，每個樣品聯合 5-FU （1：1，w/w） 處理 HT-29 結腸癌細胞均顯著降低細胞存活率。根據 Chou 和 Talalay 的藥物合併指數定理計算半抑制濃度 （IC50） 和聯合指數 （CI），5-FU / F3的組合比單獨使用 5-FU 更能發揮抑制 HT-29 細胞生長的效果及誘導凋亡，且能持續作用至 72 小時，次之為 5-FU / F1 持續至 48 小時，5-FU / LES 持續至 24 小時。F1 聯合 5-FU 的組合比其他組合在 24 小時內展現出更佳的協同效應。LES、F1 和 F3 聯合 5-FU 能藉由增加 p-β-catenin/β-catenin 比值和 GSK3β 的含量，顯著抑制 HT-29 細胞增生，且藉由增加 caspase-3 的活性及 Cleaved PARP 表現量和 bax / bcl-2 比值，促進 HT-29 細胞凋亡,，此外，5-FU / F3 的組合也可以刺激 HT-29 細胞內 ROS 累積。整體而言，本研究結果顯示，在化學治療中利用天然膳食成分聯合化學藥物在治療癌症中展現更佳的效果。使用 F1 或 F3 聯合 5-FU 處理 HT-29 細胞能達到最佳效果；但基於較低的價格及取得方便性等因素，使用 LES 作為輔助食品治療結直腸癌也是可行之策略。 5-Fluorouracil (5-FU) is the basic chemotherapeutic agent used to treat colorectal cancer, but it produces many side effects. The use of phytochemicals in combination with chemical drugs is expected to reduce side effects and improve survival of patient. Morinda citrifolia also known as Noni, has demonstrated that had antioxidant capacity and inducing apoptosis in tumor cells. The aim of this study was to investigate the effects of the supernatant of ethanolic extracts from Noni leaf (LES) and its fractions F1 and F3 (Rutin) combine with 5-FU on the cell viability, oxidative stress, and signaling transduction of colorectal cancer cell line, HT-29. The results showed that the treatment of HT-29 colon cancer cells with each samples and 5-FU (1:1, w/w) significantly all decreased cell viability. The 5-FU/F3 combination enabled a more effective inhibition of cell growth and the induction of apoptosis in HT-29 cells than 5-FU alone for 72 hours, followed by 5-FU/F1 for 48 hours and 5-FU/LES for 24 hours, according to the half inhibitory concentration (IC50) and combined index (CI) calculated by the combination-index methods of Chou and Talalay. The combination of F1 and 5-FU displayed a greater synergistic effect for 24 hour than the others combination. The combination of LES, F1 and F3 with 5-FU significantly inhibited the proliferation of HT-29 cells by increasing the p-β-catenin/β-catenin ratio and the expression of GSK3β, and promoting the apoptosis of HT-29 cells by increasing the activity of caspase-3, the expression of cleaved PARP and bax/bcl-2 ratio. Furthermore, the 5-FU/F3 combination could stimulate intercellular ROS accumulation in HT-29 cells. In conclusion, the results of this study suggest that chemotherapy using natural dietary agents with chemical agents represents a superior cancer treatment. Treatment of HT-29 cells with F3 or F1 combined with 5-FU is expected to achieve the best results. It is also possible to use LES as an auxiliary food to treat colorectal cancer cells because of lower price and accessibility.
