中藥材薏苡萃取物對免疫調控因子基因表現之調控對於腫瘤細胞與惡質化的影響

謝長堯
中國醫藥大學
薏苡為重要的中藥材和食補的材料。在先前的研究計畫中，我們以薏苡專一性作用基因蛋白質為基礎，進一步探討薏苡組成物作用機轉與臨床可能之運用方式。運用由化學系郭悅雄教授自薏苡殼甲醇萃取物中分離純化出的十多種化合物，針對我們先前由薏苡粗萃物觀察到的包含抑制腫瘤細胞促血管新生能力、抑制發炎反應分子、抑制血清誘發腫瘤細胞侵襲力。分別以VEGF、IL-6、Cox-2、MMP-9等基因作為薏苡組成物作用機轉評估標準。我們發現薏苡組成物中以目前僅在薏苡中被發現的4-ketopinoresinol(已發表於J Agric Food Chem. 2002. Kuo YH. et.al )，對腫瘤細胞IL-6、MMP-9的產生具有良好抑制作用。在機轉探討上，由細胞生長曲線與細胞週期分析，我們發現4-ketopinoresinol並無細胞毒性，它對腫瘤細胞具有延緩細胞週期G2/M的作用。此外4-ketopinoresinol會抑制血清誘發包括Akt、ERK、p38、JNK的磷酸化，也會抑制NF-kB的活性，包括抑制NF-kB進入細胞核內與結合能力。我們認為薏苡組成物對細胞內NF-kB的活性調控具有發展潛力。由於NF-kB的活性調節在免疫反應調節上具有重要角色，因此我們提出未來在九十四年度的研究計畫的第一個目標將針對薏苡對腫瘤細胞免疫調控因子基因表現之調控影響進行探討。此外我們先前針對薏苡在臨床可能之運用方式的研究上，分別以薏苡的部分攝食取代（混於飼料）、粗萃物（管餵）、純物質（腹腔注射）測試它們與具放射線治療併用的作用結果顯示薏苡的部分攝食取代最具有增強放射線治療效果的作用，結果也顯示外薏苡的部分攝食取代能降低放射線治療誘發的IL-6，此結果應與薏苡的抗發炎的效應有關，同時我們也觀察到薏苡的部分攝食取代會使得治療過程中小鼠的體重變化穩定。
關鍵字：薏苡；惡質化

Effects of Chinese herb-Adlay on inflammatorycytokine regulation- on tumor cells and cachexia

Chang-Yao Hsieh
Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine
Adlay is used as an anti-inflammatory herb in the Chinese traditional therapy. Several researches have indicated that adlay was also found to have anti-tumor properties in an animal model. Different adlay extracts were used to investigate the therapeutic effect of adlay on gynecological cancer. Ovarian cancer cell lines SKOV-3, CaoV-3 and cervical cancer cell lines SiHa, HeLa were used in our previous study. Our results showed that pure compound 4-ketopinoresinol, which has been published on Journal of Agriculture and Food Chemistry in 2002 by Kuo YH, was isolated from adlay has potential role in cancer therapy. We found that under the non-cytotoxic concentration, 4-ketopinoresinol could significantly arrest the cell cycle of both ovarian cancer and cervical cancer cell lines, attenuate the serum-induced invasion in both ovarian cancer and cervical cancer cell lines, decrease the angiogenic capability of ovarian cancer and cervical cancer cell lines on HUVEC growth and tube formation and Attenuated tumor cell intra-vasation in CAM model. 4-ketopinoresinol also shown potential effect on inhibition cancer cells IL-6 expression. Clinical evidences show that chemical or radiation therapy cause patient cachexia usually, which is a phenomenon of body weight loss in a short period of time.
關鍵字：Adlay；cachexia