博碩士論文 111223087 詳細資訊



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姓名 潘思妘(Ssu-Yun Pan)  查詢紙本館藏   畢業系所 化學學系
論文名稱
(Exploration of the Biological Functions of Bicyclic Pyrazoline Analogue, HJL-A-58A, In Vitro)
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 (2029-7-1以後開放)
摘要(中) 薑黃素是香料薑黃中的黃色色素，由於其抗增殖和抗血管生成特性而成為有前途的抗癌劑。然而，薑黃素在體內的生物利用度和功效較低，阻礙了其臨床發展。因此，我們研究了源自單羰基薑黃素類似物的雙雜環衍生物作為潛在的抗癌藥物候選者。我們的研究發現化合物HJL-A-58A是一種新型雙環吡唑啉類似物，它在MDA-MB-231、BT549、MIA PaCa-2、PANC-1和PC-3等癌細胞系中表現出抗增殖活性。此外，化合物HJL-A-58A在這五種癌細胞系中也顯示出抗遷移能力。在細胞週期實驗中，MIA PaCa-2細胞在處理化合物HJL-A-58A 48小時後，呈現劑量依賴性的S期停滯。此外，我們的研究結果表明，化合物HJL-A-58A在管形成測定及離體小鼠主動脈環實驗中皆顯示出有效的血管增生抑制活性，突顯了其在靶向腫瘤脈管系統方面的潛力。這些結果強調了HJL-A-58A透過針對細胞存活、遷移和血管生成途徑來對抗癌症進展的治療潛力。
摘要(英) Curcumin, the yellow pigment in the spice turmeric, has emerged as a promising anti-cancer agent due to its anti-proliferative and anti-angiogenic properties. However, curcumin′s low bioavailability and efficacy in vivo have hindered its clinical development. Therefore, we investigated bis-heterocyclic derivatives derived from monocarbonyl curcumin analogs as potential anti-cancer drug candidates. Our study found that compound HJL-A-58A, a novel bicyclic pyrazoline analog, exhibited anti-proliferative activity in cancer cell lines such as MDA-MB-231, BT549, MIA PaCa-2, PANC-1, and PC-3. Additionally, compound HJL-A-58A demonstrated anti-migratory capabilities in these five cancer cell lines. In cell cycle experiments, MIA PaCa-2 cells were arrested in the S phase in a dose-dependent manner after treatment with compound HJL-A-58A for 48 hours. Furthermore, our results indicate that compound HJL-A-58A shows effective angiogenesis inhibitory activity in tube formation assays and in ex vivo mice aortic ring assays, highlighting its potential in targeting tumor vasculature. These results underscore the therapeutic potential of HJL-A-58A in combating cancer progression through targeting cell survival, migration, and angiogenesis pathways.
關鍵字(中) ★ 血管新生 關鍵字(英) ★ angiogenesis
論文目次 中文摘要................................................ i
Abstract............................................... ii
Table of Contents...................................... iii
List of Figures........................................ vi
List of Tables......................................... viii
List of Abbreviations.................................. ix
Chapter I. Introduction................................ 1
1-1 Background........................................ 1
1-2 Introduction of triple negative breast cancer..... 2
1-2-1 Breast cancer and its subtypes.................. 2
1-2-2 Triple negative breast cancer (TNBC)............ 4
1-3 Introduction of pancreatic cancer................. 5
1-3-1 Pancreatic cancer and its subtypes.............. 5
1-3-2 Pancreatic ductal adenocarcinoma (PDAC)......... 6
1-4 Introduction of prostate cancer................... 8
1-4-1 Prostate cancer and its subtypes................ 8
1-4-2 Prostate adenocarcinoma......................... 9
1-5 Introduction of lung cancer....................... 10
1-5-1 Lung cancer and its subtypes.................... 10
1-5-2 Lung adenocarcinoma............................. 11
1-6 Introduction of cervical cancer................... 12
1-6-1 Cervical cancer and its subtypes................ 12
1-6-2 Cervical squamous cell carcinoma (CSCC)......... 13
1-7 Introduction of angiogenesis...................... 14
1-7-1 Angiogenesis in cancer.......................... 14
1-7-2 VEGFA/VEGFR2/Akt signaling pathway in angiogenesis ..........16
Chapter II. Results and Discussion..................... 17
2-1 Research motivation............................... 17
2-2 Anti-proliferative ability of HJL-A-58A in different cell lines..... 20
2-3 Anti-migration ability of HJL-A-58A in different cell lines.......... 24
2-4 Effects of HJL-A-58A on MIA PaCa-2 cell cycle arrest ..........27
2-5 Kinases activities of HJL-A-58A................... 29
2-6 Cytotoxicity of HJL-A-58A in HUVECs............... 31
2-7 The ability of HJL-A-58A to modulate tube formation in HUVECs......... 33
2-8 Anti-angiogenic effect of HJL-A-58A in ex vivo mice aortic ring assay...... 34
2-9 Effect of HJL-A-58A on the VEGFR2/Akt signaling pathway ..........36
Chapter III. Conclusions............................... 38
Chapter IV. Materials and Methods...................... 39
4-1 Cell line used and cell culture................... 39
4-2 MTT cytotoxicity assay............................ 41
4-3 Transwell migration assay......................... 41
4-4 Cell cycle analysis............................... 42
4-5 Tube formation analysis........................... 42
4-6 Kinase selectivity profile........................ 43
4-7 Ex vivo mice aortic ring assay.................... 45
4-8 Western blot...................................... 45
Chapter V. References.................................. 46
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指導教授 李文仁 李文山(Wen-Ren Li Wen-Shan Li) 審核日期 2024-8-20
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