Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/98015
DC FieldValueLanguage
dc.contributor林金源zh_TW
dc.contributorJin-Yuarn Linen_US
dc.contributor.author張曉青zh_TW
dc.contributor.authorSheau-Ching Changen_US
dc.contributor.other食品暨應用生物科技學系所zh_TW
dc.date2018zh_TW
dc.date.accessioned2019-03-22T06:23:23Z-
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dc.identifier.urihttp://hdl.handle.net/11455/98015-
dc.description.abstract苦丁茶 (Ilex kudingcha)為傳統天然保健飲品,具有抗氧化、抗發炎等功效。本研究室先前研究已發現苦丁茶甲醇萃取物在體外實驗中,具有免疫調節功效,且對於人列腺癌PC-3細胞有抗癌之潛力,然而,其在體內之免疫調節及抗前列腺癌效果仍不清楚,因此本研究以小鼠前列腺癌TRAMP-C1細胞進行動物體外及體內實驗,以評估苦丁茶甲醇萃取物之功效。在體外實驗模式,發現直接添加與癌症免疫療法模式下,適當濃度之苦丁茶甲醇萃取物對於小鼠前列腺癌TRAMP-C1細胞的生長有抑制效果。以不同濃度癌細胞注入皮下以建立皮下負載TRAMP-C1癌細胞之C57BL/6J雄鼠動物模式,結果發現,於皮下注射癌細胞,使C57BL/6J小鼠免疫反應傾向Th1免疫平衡;觀察小鼠腫瘤大小及腫瘤組織病理變化情形,建議以注射低濃度癌細胞 (5 × 104 cells/mouse) 經過30天之條件,最適合做為動物體內負載前列腺癌之實驗模式。 利用已建立的動物體內模式管餵苦丁茶甲醇萃取物4週,結果顯示管餵苦丁茶甲醇萃取物,使C57BL/6J雄鼠脾臟細胞及腹腔巨噬細胞細胞激素分泌,傾向抗發炎之免疫平衡。此外,苦丁茶甲醇萃取物可增加小鼠周邊血液淋巴世系細胞分布比率,增加其免疫能力。觀察腫瘤組織病理變化發現,給予苦丁茶甲醇萃取物能改善腫瘤惡化情形;癌症指標結果顯示,給予小鼠中劑量 (200 mg/kg b.w./day) 樣品能降低血清中TNF-α濃度,管餵中劑量、低劑量 (50 mg/kg b.w./day) 樣品可降低小鼠血清中前列腺癌專一性抗原PSA濃度。 綜合本實驗結果,苦丁茶甲醇萃取物在體外實驗中,能透過直接與間接免疫調節作用抑制小鼠前列腺癌TRAMP-C1細胞之生長;在體內實驗中,苦丁茶甲醇萃取物使皮下負載TRAMP-C1癌細胞之C57BL/6J小鼠免疫反應傾向Th2免疫平衡,降低體內發炎細胞激素之分泌,並增加周邊血液淋巴球分布比例,改善免疫功能而達到抑制腫瘤生長之效果,具有抗前列腺癌之潛力。zh_TW
dc.description.abstractIlex kudingcha, serving as a traditional natural health drink, has antioxidant and anti-inflammatory effects etc. In our preliminary studies, Ilex kudingcha methanol extract (IKME) has immunomodulatory effects and anti-cancer potential for human prostate carcinoma PC-3 cells in vitro. However, immunomodulatory and anti-prostate cancer effects of IKME in vivo are still unclear. To unravel the puzzle, mouse prostate cancer TRAMP-C1 cells were used to investigate the effects of IKME in vitro and in vivo. In vitro, we found that IKME at an appropriate concentration had anti-cancer effects against the growth of TRAMP-C1 cells via either direct addition or cancer immunotherapy. To establish an animal model for evaluating IKME effects on TRAMP-C1 cells in vivo, C57BL/6J male mice were injected subcutaneously with different concentrations of TRAMP-C1 cells for different days. The results showed that C57BL/6J male mice subcutaneously loaded with TRAMP-C1 cells had Th1-inclination immune balance. Based on tumor sizes and pathological changes of tumor tissues in the experiment mice, it is recommended that C57BL/6J male mice that are subcutaneously injected with low dose cancer cells (5 × 104 cells/mouse) for 30 days is the most suitable animal model for subsequent experiments in vivo. Using the established animal model, IKME was administered to the experiment animal by gavage for 4 weeks. It was found that IKME administration resulted in anti-inflammatory effects according to cytokine secretion profiles by splenocytes and peritoneal macrophages of C57BL/6J male mice subcutaneously loaded with TRAMP-C1 cancer cells, respectively. Besides, IKME administration increased the percentage of lymphoid lineage cells in peripheral blood, enhancing their immunity of the experiment animals. Observation of pathological changes in tumor tissues indicated that IKME might improve the status of tumor deterioration. Evaluation on carcinogenic markers showed that medium (200 mg/kg b.w./day ) doses of IKME administration reduced serum TNF-α concentration in the experiment mice. Medium and low dose (50 mg/kg b.w./day ) of IKME administration significantly lowered serum prostate cancer specific antigen (PSA) concentration. In conclusion, IKME administration in vitro could inhibit the growth of mouse prostate cancer TRAMP-C1 cells through either direct addition or indirect immunotherapy. In vivo, IKME administration tended to have a Th2-inclination immune balance in C57BL/6J mice subcutaneously loaded TRAMP-C1 cancer cells. IKME administration reduced pro-inflammatory cytokine secretions in the body, but increased the distribution of peripheral blood lymphocytes. Furthermore, IKME administration might improve the necrotic status in tumor tissues via increasing the immunity of the experiment mice. IKME has the potential to resist prostate cancer in vitro and in vivo.en_US
dc.description.tableofcontents摘要 i Abstract ii 目錄 iv 圖目次 vii 表目次 ix 縮寫對照表 x 緒言 1 第一章 文獻回顧 2 第一節 免疫系統的組成 2 一、先天性免疫系統 (innate immune system) 2 二、適應性免疫系統 (adaptive immune system) 2 第二節 Th1/Th2免疫平衡及發炎反應 4 第三節 免疫反應與癌症 6 第四節 前列腺癌 8 第五節 苦丁茶 (Ilex kudingcha) 9 一、苦丁茶的成分 9 二、苦丁茶的藥理療效 9 第六節 研究動機與目的 11 第七節 實驗設計 11 第二章 苦丁茶甲醇萃取物對小鼠前列腺癌TRAMP-C1細胞株生長之影響 12 第一節 前言 12 第二節 材料與方法 12 一、本章實驗架構如下 12 二、樣品製備 13 三、小鼠前列腺癌TRAMP-C1細胞株之培養 14 四、小鼠前列腺癌TRAMP-C1細胞株倍增時間試驗 16 五、苦丁茶甲醇萃取物之初代脾臟細胞條件培養液製備 17 六、苦丁茶甲醇萃取物之初代巨噬細胞條件培養液製備 20 七、 苦丁茶甲醇萃取物與條件培養液對小鼠前列腺癌TRAMP-C1細胞株生長之影響 22 第三節 結果 25 一、小鼠前列腺癌TRAMP-C1細胞株倍增時間 (doubling time) 計算 25 二、苦丁茶甲醇萃取物與其處理之免疫細胞條件培養液對小鼠前列腺癌TRAMP-C1細胞株生長之影響 26 第四節 討論 31 第五節 結論 32 第三章 建立皮下負載TRAMP-C1癌細胞之C57BL/6J 雄鼠動物實驗模式 33 第一節 前言 33 第二節 材料與方法 33 一、本研究實驗架構如下 33 二、實驗動物飼養、分組與前列腺癌植入實驗模式 34 三、小鼠犧牲後測定項目 35 四、脾臟與腹腔細胞之細胞激素含量測定 36 五、血液取得與分析 41 六、腫瘤組織切片 45 七、統計分析 45 第三節 結果 46 一、皮下負載不同濃度TRAMP-C1癌細胞對C57BL/6J雄鼠體重及臟器之影響 46 二、 皮下負載不同濃度TRAMP-C1癌細胞對C57BL/6J雄鼠免疫反應之影響 50 三、 皮下負載不同濃度TRAMP-C1癌細胞對C57BL/6J雄鼠癌化指標之影響 55 第四節 討論 64 第五節 結論 66 第四章 苦丁茶甲醇萃取物對前列腺癌模式小鼠體內免疫反應及癌化指標變化之影響 67 第一節 前言 67 第二節 材料與方法 67 一、本研究實驗架構如下 67 二、試驗飼料配製 68 三、實驗動物飼養、分組與前列腺癌模式 70 四、犧牲後測定項目 71 五、脾臟與腹腔細胞之細胞激素含量測定 72 六、血液取得與分析 73 七、腫瘤組織切片 77 八、統計分析 77 第三節 結果 78 一、 不同劑量苦丁茶甲醇萃取物管餵4週對皮下負載TRAMP-C1前列腺癌細胞C57BL/6J小鼠體重及臟器之影響 78 二、 不同劑量苦丁茶甲醇萃取物管餵4週對皮下負載TRAMP-C1前列腺癌細胞C57BL/6J小鼠免應反應之影響 82 三、 不同劑量苦丁茶甲醇萃取物管餵4週對皮下負載TRAMP-C1前列腺癌細胞C57BL/6J小鼠癌化指標之影響 93 第四節 討論 103 第五節 結論 105 第五章 總討論與總結 106 第六章 參考文獻 107zh_TW
dc.language.isozh_TWzh_TW
dc.rights同意授權瀏覽/列印電子全文服務,2021-08-30起公開。zh_TW
dc.subject癌症免疫療法zh_TW
dc.subject苦丁茶甲醇萃取物zh_TW
dc.subject小鼠前列腺癌細胞TRAMP-C1zh_TW
dc.subjectCancer immunotherapyen_US
dc.subjectIlex kudingcha methanol extracten_US
dc.subjectMouse prostate cancer TRAMP-C1 cellsen_US
dc.title管餵苦丁茶甲醇萃取物對皮下負載TRAMP-C1癌細胞之C57BL/6J雄鼠體內免疫反應及癌化指標變化之影響zh_TW
dc.titleEffects of Ilex kudingcha methanol extracts on immune responses and carcinogenic markers in male C57BL/6J mice subcutaneously loaded with TRAMP-C1 cancer cellsen_US
dc.typethesis and dissertationen_US
dc.date.paperformatopenaccess2021-08-30zh_TW
dc.date.openaccess2021-08-30-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypethesis and dissertation-
item.cerifentitytypePublications-
item.fulltextwith fulltext-
item.languageiso639-1zh_TW-
item.grantfulltextrestricted-
Appears in Collections:食品暨應用生物科技學系
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