第一型拓樸異構酵素抑制劑吳茱萸鹼在具有抗藥性細胞之生物活性探討

Effects of topoisomerase I inhibitor evodiamine on drug resistant cells

楊千醇(Chien-Chun Yang)

指導教授 ： 林俊茂

臺北醫學大學/醫學院/醫學科學研究所/碩士(2012年)

https://doi.org/10.6831/TMU.2012.00019

摘要

卵巢癌是婦科常見的癌症之一，通常早期發現會有不錯的治癒率。但是由於大部份的卵巢癌在早期都沒有明顯的症狀，所以大部份的婦女當被發現是卵巢癌的時候，通常都已經擴散，成為較晚期的癌症，因此卵巢癌的死亡率相當高。目前對於卵巢癌的治療方式除了手術切除以及放射線治療外，就是化學藥物治療法，但在晚期的卵巢癌患者經常對於藥物產生抗藥性，而失去了治療的效果。因此抗藥性問題一直日前學術研究上積極探討的方向。本研究室先前已證實吳茱萸之有效成分EVO對CPT抗藥株A2780R2000人類卵巢癌細胞具有毒殺的效果，我們進一步透過建立抗藥性卵巢癌模式鼠，並使用此模式探討EVO在生物體內的活性。實驗結果證實在抗藥性卵巢癌模式鼠中EVO能夠有效抑制腫瘤的生長。除了其在真核細胞的影響，我們還討論了對原核細胞的影響。因為臨床細菌越來越對常規的抗生素具有耐藥性，產生多重抗藥性問題，對於公眾健康產生莫大的風險。結果顯示EVO對於從臨床分離的克雷伯式肺炎菌的最低抑制菌生長的抗生素濃度與抗生素 (MIC= ＞512 μg/mL)相比較低(MIC= 128 μg/mL)。結果表明了EVO為有發展淺力的抗菌劑。

關鍵字

吳茱萸鹼 ； 拓樸異構酶抗藥株 ； 克雷伯式肺炎菌

並列摘要

Ovarian cancer is one of the most common cancers in obstetrics & gynecology. It is curable when found early, but because it does not cause any symptoms in its early stages, most women have already the cancer in metastasis stage at the time of diagnosis. Therefore, the mortality rate from ovarian cancer exceeds that for all other gynecologic malignancies combined. Surgery is the initial treatment of choice, and patients may be given chemotherapy if who are not fit for surgery. Although chemotherapy drugs often prove effective in managing or treating cancer growth, acquired drug resistance frequently hampers efficient chemotherapy of cancers. Our laboratory has confirmed the cytotoxic effect of evodiamine (EVO) against the camptothecin (CPT)-resistant strains of A2780R2000 human ovarian cancer cell. We further establish the drug-resistant ovarian tumor xenograft model and evaluate the EVO activity in this animal model. The EVO repressed the tumor growth effectively in the tumor xenograft SCID mice. In addition to its effect on eukaryotic cells, we also addressed the ffects on prokaryotic cells because clinical bacteria are increasingly resistant to conventional antibiotics and multi-drug resistant Gram-negative bacteria confer the greatest risk to public health. EVO showed a significantly lower minimal inhibitory concentration value (MIC, 128 μg/mL) in comparison with antibiotics (> 512 μg/mL) against clinical isolates K. pneumoniae. The results suggest EVO having potential to develop a bactericidal agent.

並列關鍵字

Evodiamine ； topoisomerase ； drug resistant cells ； Klebsiella pneumoniae

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