結直腸癌為台灣癌症相關死亡原因的第三名。為了提高癌症預後，臨床治療多使用化療；但化療對正常組織所產生的毒性，已嚴重阻礙癌症的治療效果。故在化療過程中給予適當的輔助療法，減緩病人的不適，不僅可提高治癒機會，也減少化療藥物的毒性。5-FU一直是治療結直腸癌的主要化療藥物，但治療效綠一直維持在 20-35%，其中位數存活率不超過 1年。 因此，尋找具有高保健功效的抗癌成分，並與化療藥物組合運用，用以提高更好的治療效果，是治療結直腸癌的新興發展方向。研究顯示發炎反應和氧化壓力與腫瘤發生間存在顯著相關，虎杖根部乙醇萃取物分劃物 (PcE(H)EA) 含有多樣化與高含量的多酚類物質，具有抗發炎和抗氧化生物活性，值得進一步純化與評估防癌功效。第一年探討 PcE(H)EA 內活性成分聯合 5-FU 對結直腸癌細胞 (HT-29) 的體外抑制作用與作用機制。第二年使用發炎引起的結直腸癌動物模型，評估實驗樣品預防結直腸癌發生的效果。第三年使用 HT-29 細胞異種移植在裸鼠體內，將實驗樣品、5-FU 或兩者組合，分別管餵裸鼠，觀察腫瘤異種移植後的抑制效果。這些研究將闡明 PcE(H)EA 抗癌的作用機制與效能，未來可用於預防結直腸癌，或結合傳統化療，增加其療效；這是可行的輔助治療策略，兼具避免化療藥物被腫瘤細胞快速發展成抗性。 Colorectal carcinoma is the third leading cause of cancer-related death in Taiwan. In order to improve the prognosis, chemotherapy is often used in a variety of clinical situations. The toxicity of these chemotherapeutic agents to normal tissues has been one of the major obstacles to successful cancer chemotherapy. Therefore, combined treatments with adjuvant therapy are often used not only to enhance the treatment effect, but also to reduce the toxicity of these drugs. 5-fluorouracil (5-FU) has been the major chemotherapeutic agent for treating colorectal carcinoma; however, response rates have been around 20–35% with median overall survival no more than 1 year. So finding anti-cancer compounds with high nutraceutic effect which can be used in combination with existing drugs may provide an important way forward in the treatment of colorectal carcinoma. The connection between inflammation / oxidative stress and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Based on our researches, fractionation in ethanolic extracts from Polygonum cuspidatum root (PcE(H)EA) exhibit various and higher contents in polyphenols, and reveal that these compounds play a part in antioxidative and anti-inflammatory activity in vitro. Hence, PcE(H)EA and its active components are worth further research in purification, and deeply investigation for anti-cancer effects. The first study aim to investigate the inhibitive effects of active components from PcE(H)EA combined with 5-FU on colorectal carcinoma (HT-29) cells in vitro, and the relative molecular mechanisms. The objective of the second study is to evaluate the chemopreventive effects of test sample in vivo. A animal model of colitis-associated colorectal cancer will be employed to determine the effect of test sample. The third study is to investigate test sample for enhancement of the chemotherapeutic effect of 5-FU for colorectal cancer in vivo. The model of tumour xenografts will be established in nude mice. Test sample and 5-FU, either in combination or on their own, are gavaged into mice and the inhibition effects of cell proliferation will be observed. These studies will elucidate the possible molecular mechanisms and therapeutic efficacy of PcE(H)EA for anti-cancer. Moreover, PcE(H)EA can be used to prevent and treat colorectal cancer might be combined with conventional therapies, such as chemotherapy, to increase their efficacy. This is a very practicable strategy of adjuvant therapy—they might avoid the rapid development of resistance that occurs to drugs that target cancer cells.
