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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林淑萍 | |
dc.contributor.author | Hung-Wei Pan | en |
dc.contributor.author | 潘宏韋 | zh_TW |
dc.date.accessioned | 2021-06-12T18:26:36Z | - |
dc.date.available | 2016-10-07 | |
dc.date.copyright | 2011-10-07 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-08 | |
dc.identifier.citation | 1. Provencio M, Sanchez A, Garrido P, Valcarcel F. New molecular targeted therapies integrated with radiation therapy in lung cancer. Clin Lung Cancer 2010;11:91-7.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/27896 | - |
dc.description.abstract | 肺癌為全世界當前發生頻率最高且預後差的癌症,其高致死率使它近年來竄升為台灣癌症死亡原因的首位。絕大部分肺癌病患被診斷患病時多屬於晚期,此時病患已無法靠手術治癒,只能接受化學治療,或輔以放射線與標靶藥物治療;但臨床治療的困境是藥物常因其藥物毒性而使得投藥濃度受到相當大的侷限,且在治療後會產生抗藥性。因此為了能更有效的治療肺癌,發展新的治療藥物或是將現有之藥物輔以佐劑(adjuvant)以達到更好之治療效果為當前熱門的研究方向。靈芝是一種在亞洲國家被廣泛使用的傳統中藥,而其中的許多成分已有研究證實具有抗癌的功效。本研究主要目的是想探討靈芝萃取物T-612作用於肺腺癌細胞之抗癌效果。T-612之抗癌效果研究分為兩個方向:(1)作為肺癌治療藥物之佐劑。(2) 作為抗標靶藥物艾瑞莎之肺癌治療藥物。實驗結果顯示:(1) 在體外的實驗(in vitro),將T-612與各種癌症化療常用藥物合併處理PC9細胞株,發現T-612與VP-16 (Topoisomerase II poison)合併使用能加強VP-16的抗癌活性(IC50=1.99 μM 降至0.51 μM),且使細胞週期滯留在G2/M期的細胞顯著增加,最終造成細胞凋亡。同時也觀察到合併處理的實驗組可以促進活性氧化物(reactive oxygen species, ROS)的累積。將PC9細胞株接種於免疫缺陷小鼠皮下進行活體實驗(in vivo)發現,VP-16與T-612結合餵食比單獨使用VP-16更能有效抑制腫瘤生長。總和以上結果,本部分研究從體外細胞實驗與體內動物實驗皆證實了T-612具有潛力可以做為VP-16的佐劑。(2) 以T-612處理PC9及抗艾瑞莎之PC9IR肺癌細胞,觀察到T-612能夠抑制兩種細胞株的生長,且具有毒殺的效果 (PC9: IC50=8.1 μM ; PC9IR: IC50=4.4 μM, 72 h)。PC9IR細胞經過T-612處理後,我們發現細胞形態變圓且爬行能力(migration ability)降低;分析細胞內的變化情形,發現T-612會造成活性氧ROS堆積,且最終細胞走向細胞凋亡。 | zh_TW |
dc.description.abstract | Lung cancer is one of the most common malignant diseases worldwide and it has become the leading cause of cancer-related mortality over the past years in Taiwan. Most lung carcinomas are diagnosed at an advanced stage, conferring a poor prognosis. If the tumor is aggressive, chemotherapy, radiotherapy and targeted therapy may be used in addition to or instead of surgery. But most of chemotherapeutic drugs are too toxic for human clinical use, and most patients who initially respond to targeted drugs will develop resistance. Therefore, providing an effective treatment for lung cancer is essential. Ganoderma (Lingzhi) as a well-known traditional Chinese herb has been used for medicinal purposes for centuries in Asia. There are many bioactive compounds have been reported as anticancer ingredients of the medical mushroom. We investigated the anti-cancer activities of T-612, a compound from Ganoderma tsugae Murr. (YK-01), to against the non-small cell lung cancer cells. The aim of our research is to develop T-612 as an (i) adjuvant for chemotherapeutic drugs and (ii) anticancer agent. (i) For T-612 as an adjuvant, T-612 was combined with other anticancer drugs. We found that T-612 enhanced anticancer activity of VP-16 through mitotic arrest and then induced apoptosis. In addition, we found that cyclin B1, Cdc25c and p21 expression level was modulated after combination treatment of VP-16 and T-612. ROS accumulation was also observed. Furthermore, the combination was also more effective than either single agent in inhibiting the growth of lung cancer xenografts in mice. (ii) Our data revealed that T-612 displayed growth inhibitory effects on both PC9 cells and Iressa-resistant PC9IR cells, Besides, T-612 could inhibit migration of PC9IR cells. The mechanism of T-612–induced cytotoxicity was through induction of reactive oxygen species (ROS)
and led to apoptosis. These results suggest that T-612 is an effective adjuvant of VP-16 and potential anticancer agent. | en |
dc.description.provenance | Made available in DSpace on 2021-06-12T18:26:36Z (GMT). No. of bitstreams: 1 ntu-100-R98424028-1.pdf: 3311527 bytes, checksum: c5099913cb77d1f6a071d55c16125f83 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 摘要 i
Abstract iii 目錄 v 圖目錄 viii 1. 研究背景 1 1.1. 肺癌 (Lung Cancer) 1 1.1.1. 肺癌的分類 1 1.1.2. 非小細胞肺癌的分期 1 1.1.3. 非小細胞肺癌的治療 2 1.2. 靈芝 (Lingzhi, Ganoderma) 4 1.3. 細胞週期 (Cell Cycle) 5 1.4. 細胞凋亡 (Apoptosis) 6 1.4.1. 外源性途徑 (Extrinic Apoptosis Pathway) 6 1.4.2. 內源性途徑 (Intrinic Apoptosis Pathway) 6 1.5. 滅必治 (Etoposide) 7 1.6. 自由基 (Free Radical) 7 1.6.1 活性氧化物 (Reactive Oxygen Species, ROS) 8 1.6.2 抗氧化機制 9 1.6.3. 活性氧化物與癌症治療 9 2. 研究目標 11 第一部分 12 3. 材料與方法 13 3.1. 細胞培養 13 3.2. 細胞活性測定 13 3.3. 細胞週期分析 (Cell cycle analysis) 13 3.4. 細胞內活性氧化物測定 14 3.5. 胞落形成試驗 (Colony formation assay) 14 3.6. 西方墨點法 (Western blotting) 14 3.7. 異種移植腫瘤模式 (Xenograft tumor model) 15 3.8. 病理組織處理及染色 16 3.8.1 病理組織處理 16 3.8.2. Hematoxylin & Eosin stain (H&E stain) 16 3.9. 小鼠血液常規檢查 (Complete blood count) 16 3.10. 統計分析 17 4. 結果 18 4.1. T-612顯著地促進VP-16對PC9細胞株之抗癌活性 18 4.2. T-612合併VP-16使細胞停滯在分裂期(mitotic arrest)後誘導細胞凋亡發生 19 4.3. T-612結合VP-16處理細胞48小時後會造成活性氧化物累積 20 4.4. 動物實驗亦證實T-612可以顯著地促進VP-16之抗癌效果 20 5. 討論 22 6. 圖 25 第二部分 34 7. 材料與方法 35 7.1. 細胞培養 35 7.2. Trypan blue exclusion assay 35 7.3. 細胞凋亡分析 35 7.4. 細胞粒線體膜完整性測定 35 7.5. 細胞內Caspase活性測定 36 7.6. 細胞傷口癒合試驗 (Wound healing assay) 36 7.7. 細胞穿孔移動能力試驗(Transwell migration assay) 36 7.8. 統計分析 37 8. 結果 38 8.1. T-612有效地抑制對於艾瑞莎有抗性的肺癌細胞PC9IR的生長 38 8.2. T-612處理先抑制細胞生長但不造成早期細胞膜損傷,最後導致細胞死亡 38 8.3. T-612使氧化壓力上升,造成細胞之內源性細胞凋亡 39 8.4. T-612處理會抑制細胞爬行能力 40 9. 討論 41 10. 圖 43 11. 參考資料 51 12. 附錄 58 13. 材料清單 60 | |
dc.language.iso | zh-TW | |
dc.title | 靈芝萃取物T-612對非小細胞肺癌細胞株之抗癌活性研究 | zh_TW |
dc.title | Studies on the Anticancer Activity of T-612 from Ganoderma in NSCLC Cell Lines | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林亮音,楊雅倩,胡忠怡 | |
dc.subject.keyword | 肺癌,靈芝,細胞凋亡,活性氧化物,VP-16,細胞週期停滯, | zh_TW |
dc.subject.keyword | Lung cancer,Ganoderma,apoptosis,ROS,VP-16,mitotic arrest, | en |
dc.relation.page | 61 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-08 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-100-1.pdf 目前未授權公開取用 | 3.23 MB | Adobe PDF |
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