狼尾草萃取物之抗腫瘤活性

Taipei Medical University Institutional Repository > 營養學院 > 保健營養學系暨研究所 > 博碩士論文 > Item 987654321/59502

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題名:	狼尾草萃取物之抗腫瘤活性 The antitumor potential of Pennisetum purpureum S. extracts
作者:	許思瑜 Hsu, Ssu-Yu
貢獻者:	吳啟豪
關鍵詞:	非小細胞肺腺癌;天然植物化合物;狼尾草 lung adenocarcinoma cancer;phytochemicals;Pennisetum purpureum S.
日期:	2015-07-09
上傳時間:	2020-08-31 11:19:48 (UTC+8)
摘要:	非小細胞肺腺癌 (non-small cell lung adenocarcinoma, NSCLC)為肺癌中最常見且惡性程度最高的型態。源自天然草本之植物化合物 (phytochemicals)因具有多重保健機能性，相較於化學合成藥物，應用於臨床治療上有較低的副作用，具有發展為抗癌輔助藥物之潛力。本研究擬探討台灣原生種狼尾草台畜草二號 (Pennisetum purpureum S. of extracts, PPE)之萃取物，運用人類腫瘤異種移植 (human xenograft tumor models)之動物模式評估狼尾草萃取物對人類肺腺癌之抗腫瘤活性。利用pGL4.51[luc2/CMV/Neo]質體進行目標細胞轉殖，建立luciferase reporter gene穩定表現之人類肺腺癌H441基因轉殖株 (H441-luc)，搭配非侵入式活體分子影像系統 (Caliper IVIS system)與micro-CT (SkyScan1176)進行活體之腫瘤評估。異位肺癌動物模式 (heterotopic lung tumor animal model)結果顯示，連續五週投予劑量為100及200 mg/kg b.w.之PPE可抑制BALB/c nu/nu mice皮下腫瘤77 %生長，顯示PPE具有延緩NSCLC增生之實質生理意義。進一步以原位肺癌動物模式 (orthotopic lung tumor animal model)，模擬原發性肺部腫瘤之病理狀態，評估連續四週投予PPE (25–100 mg/kg b.w.)之腫瘤抑制效應。結果顯示，PPE可有效延緩BALB/c nu/nu mice原發性肺腺癌腫瘤32 %之增生，並顯著提升腫瘤鼠49 %之存活率。肺部病理組織染色 (H&E staining)顯示PPE可誘發腫瘤細胞死亡。免疫組織染色更證實PPE可降低腫瘤增生蛋白ki67 (56 %)與細胞增生調控蛋白NF-kB (47 %)表現，並促進細胞凋亡調控蛋白p53 (73 %)與M30 (69 %)之表現，顯示PPE可透過調控ki67、NF-κB、p53與M30蛋白表現以誘導細胞走向凋亡表現其腫瘤效應。此外，PPE可抑制肺腺癌細胞株H441與A549之增生 (IC50分別為41.1 μg/mL及67.7 μg/mL)，然而對人類正常子宮平滑肌細胞 (uterine smooth muscle cells, utsmc)則無毒性影響，顯示PPE對細胞具選擇性毒殺效應。綜合上述，PPE可抑制活體腫瘤及肺腺癌細胞之增生，希冀未來可發展為抗癌藥物或用以輔助癌症治療之潛力。 Non-small cell lung cancer (NSCLC) is the leading cause and one of the most malignant form of lung cancer. Compared to chemotherapy drugs, the bioactive compounds isolated from natural herbs have multi-functions and less side effects. Pennisetum purpureum S. is a natural herbs and have potential for development of chemotherapy drugs. The purpose of this study was to evaluate the anti-tumor effects of extracts from Pennisetum purpureum S. (PPE) against human lung adenocarcinoma in human xenograft tumor models. We firstly transfected the pGL4.51 [luc2/CMV/Neo] into human lung adenocarcinoma cell H441 to complete the construction of H441-luc. Then we use non-invasion imaging system (Caliper IVIS system) and micro-CT (SkyScan1176) to measure the tumor development. In the heterotopic lung tumor animal model, treatment of PPE (100 and 200 mg/kg b.w.) significantly inhibited 77 % subcutaneous tumor growth. We further investigate the effect of PPE in orthotopic animal model to imitate primary lung tumor site, and we found that treatment of PPE (25–100 mg/kg b.w.) for 4 weeks inhibited 32 % tumor size and prolonged 49 % survival of tumor-bearing nude mice. H&E staining demonstrated that PPE treatment increased lung tumor tissue induction of apoptosis. Immunohistochemistry staining showed PPE decreasing the expressions of Ki-67 (56 %) and NF-κB (47 %) and increasing the expressions of apoptosis-related proteins M30 (69 %) and p53 (73 %). In addition, PPE exhibited cytotoxicity on lung cancer cells H441 (IC50 = 41.1 μg/mL) and A549 (IC50 =67.7 μg/mL) but not on normal human cell Utsmc (uterine smooth muscle cells) in vitro. Collectively, PPE have selective cytotoxicity in vitro. To the best of our knowledge, this is the first study with evidence that PPE acts as a novel chemopreventive agent in the treatment of lung tumorigenesis.
描述:	碩士指導教授:吳啟豪委員:江文章委員:夏詩閔
資料類型:	thesis
顯示於類別:	[保健營養學系暨研究所] 博碩士論文

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