查詢結果分析
來源資料
相關文獻
- 以大黃素(Emodin)調控細胞中DNA修補酵素活性及其具組織特異性之超微粒製劑在抗肝細胞腫瘤上的應用
- Solamargine對肝癌細胞之作用機轉及其具器官導向之超微粒製劑在抗肝細胞腫瘤上的應用
- 建立Acid Phosphatase酵素分析方法大量篩選天然物之抗癌藥
- Cytotoxicity of Food Mycotoxins, Natural Food Additives and Natural Aromas in Primary Cultured Rat Hepatocytes
- 大黃及其有效成分(Emodin)對糖尿病腎病變治療效果之研究
- 大黃抑制幽門螺旋桿菌及其作用機轉之研究
- 根尖充填材對人類牙齦造纖維細胞之毒性效應
- 長期葉酸消耗對人類肝癌細胞株HepG2之細胞生長繁殖及形態變化的影響
- 乙型轉型因子對於肝癌細胞死亡的調控與機制之研究
- AH26與AH plus根管充填劑對口腔癌細胞株之毒性研究
頁籤選單縮合
題 名 | 以大黃素(Emodin)調控細胞中DNA修補酵素活性及其具組織特異性之超微粒製劑在抗肝細胞腫瘤上的應用=Role of Emodin in the Regulation of DNA Repair Enzymes in Cells and the Application of Tissue-Specific Nanosphere Preparation in the Therapy for Hepatocellular Carcinoma |
---|---|
作 者 | 郭國華; | 書刊名 | 中醫藥年報 |
卷 期 | 16:2 1998.05[民87.05] |
頁 次 | 頁109-134 |
分類號 | 414.33 |
關鍵詞 | 大黃素; 超微粒子; 肝癌細胞; 細胞毒性; DNA修補作用; Emodin; Nanoparticle; Hepatocellular carcinoma; Cytotoxicity; DNA repair; |
語 文 | 中文(Chinese) |
中文摘要 | 癌症為臺灣第一大死亡原因,其發生率有逐年增加的趨勢,目前癌 症的治療可藉助外科手術與化學療法,但有些癌灶生於較高危險之區域而 不易接近或癌灶已經漫延至其它部位,故無法以外科手術切除。採用一般 化學療法治療癌症實際上並無法有意義的降低其死亡率,尤其引起全身性 的副作用常使患者捨去治療的意願。因此研究降低藥物的副作用,增加藥 物對器官之專一性,對改善癌症的治療將有很大的助益。 癌的發生原因已被研究很多,基本上均與細胞基因之突變有關,例 如肝癌、肺癌、膀胱癌、乳癌、胰臟癌及其他癌症均可發現細胞染色體 DNA 有變異現象,因此DNA變異是造成細胞癌化的直接因素。但是細胞 中具有自動修補DNA變異的能力,這些DNA修補酵素穿梭染色體中能認 識變異位置並修補入正確的DNA序列,因此具有預防細胞癌化的功能。 本計畫所用之大黃素(Emodin)已有報告具有抗腫瘤及抗突變的作用,但 其機轉尚不清楚。另一方面,藥劑學上之超微粒子(Nanosphere)具有組 織及器官的特異性,特定大小的含藥粒子能經由血流送至特定的器官,細 胞再經由吞噬作用(Phagocytosis)將藥物送入細胞中而達到治療的效 果。因此本計畫的目的:(1)製備Emodin超微粒製劑並應用於人類肝癌 細胞以評估其應用上的潛力。(2)探討Emodin對人類細胞中DNA修補 系統的影響及其抗腫瘤機轉。在本計畫的實驗結果,發現Emodin對肝癌 細胞(Hep3B)皮膚纖微母細胞與正常細胞均有毒性(WI-38)。經製備成 Emodin超微粒子並以Coulter counter測量其粒徑,其中92%以上之超微 粒子均約為180±15nm,顯示粒徑均勻一致,且此粒徑大小已有報告對 肝細胞具有特殊的親和力。經熱分析試驗結果,Emodin與超微粒子之 Polymers並不會引起交互作用而影響Emodin之藥效。將Emodin超微粒 子溶解後以HPLC測定其藥物含量為28.5 ug/ml。經實際評估Emodin超 微粒子製劑與單純Emodin對正常細胞與肝癌細胞之細胞毒性結果, Emodin超微粒子的藥效可達等劑量單純Emodin之300倍以上,顯示超微 粒子確實能有效改善Emodin作用細胞的能力,而可在極低劑量下即可有 預期的效果。因此Emodin超微粒子低劑量的使用同時配合較具器官導向 性(Target specificity)對降低該藥物所引起的副作用將有幫助。另一方 面,Emodin除了有上述抗腫瘤作用外,亦可顯著提高對UV-induced DNA damage之細胞DNA修補能力,隨著Emodin濃度增加而有逐漸增強的作 用。其詳細影響細胞DNA修補酵素之作用機轉即將完成。 |
英文摘要 | Hepatocellular carcinoma (HCC) is a predominant malignancy in Taiwan. Some anticancer drugs inhibit tumor growth by blocking cell cycle. However, the tumor cells are recovered once the anticancer drug is eliminated. Treatment of tumors in patients remains principally by surgery and chemotherapy. Because of lacking target specificity of anticancer drugs, the dosage of drug is usually elevated in order to achieve appropriate concentration in blood stream. This raising dosage of anticancer drug consequently generates severe side effects on normal tissues. By developing target-specific preparation, the side effects induced by cancer therapy may be improved. The carcinogenesis is wildly investigated in the world. In general, there are all related with the mutations on particular genes. The chromosomal mutations in several cancers, e.g., hepatoma, lung cancer, bladder cancer, breast cancer, pancreatic cancer and other cancers have been identified. These chromosomal mutations may be the important factors that causing cancers. DNA-repair enzymes recognize chromosomal mutation and restore correct sequence. This effect prevents carcinogenesis in cells. The functions of anticancer and antimutagenesis of emodin has been reported. On the other hand, the particular size of drug-coated nanoparticles are enable to be transferred to liver, and the particles are then entered the liver cells by phagocytosis. There are two aims in the proposal:(1). Evaluation and application of emodin-nanoparticle in the therapy of human hepatoma cell (2). Studies of the effect of emodin in the regulation of DNA-repair enzymes and the mechanism of anticancer activity of emodin. The results indicate that emodin possesses cytotoxicities to human hepatoma cell (Hep3B), skin fibroblast and normal lung fibroblast (WI-38). The emodin-nanoparticle was prepared according to previous report. The diameter of the particle (more than 92%) was estimated to be 180 ± 15 nm by Coluter counter, suggesting the consistency of the particles. In addition, the polymer matrix of particle was evidenced no cross-reaction with emodin. The emodin content in the nanoparticle was calculated to be 28.5 ug/ml by HPLC. It demonstrated that the potency of emodin-nanoparticle was 300-fold higher than that of equal amount of emodin. This implies that the features of low dose usage and target-specific of emodin-nanoparticle may reduce side effects of emodin in cancer therapy. In addition to the effect of anticancer activity, emodin promotes the capacity of DNA-repair for UV-induced DNA damage with a dose-dependent manner. The real mechanism of the regulation of DNA- repair enzymes is accomplished. |
本系統中英文摘要資訊取自各篇刊載內容。