Benzodiazepinedione 化合物對乳癌腫瘤生成的抑制效果

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標題:	Benzodiazepinedione 化合物對乳癌腫瘤生成的抑制效果 The inhibitory effect of Benzodiazepinedione derivatives on breast tumorigenesis Benzodiazepinedione 為許多藥物的基礎結構，然而目前有關 benzodiazepinedione 家族化合物之抗癌活性的研究報導甚為稀少。本篇研究合成了一些 1,4-benzodiazepine-2,5-dione 衍生物，並測試它們的抗腫瘤活性。結果顯示在洋菜膠腫瘤細胞群落形成試驗中，有五種 1,4-benzodiazepine-2,5-dione 衍生物會顯著地抑制纖維母細胞所調節之乳癌細胞 MDA-MB-468 的腫瘤形成。細胞存活率試驗結果顯示其中含有氯官能基和溴官能基的兩種 1,4-benzodiazepine-2,5-dione 衍生物，對 MDA-MB-468的存活率有著顯著地抑制效果，但也對纖維母細胞和非癌症的正常上皮細胞 M10 具有抑制毒性。兩種甲基化的 1,4-benzodiazepine-2,5-dione 衍生物也會顯著地抑制 MDA-MB-468 的存活率，但它們對纖維母細胞和 M10 細胞的存活率不太具有抑制的活性。此外，在與抗癌藥物 doxorubicin 合併使用的測試中，不外接官能基修飾的 1,4-benzodiazepine-2,5-dione 可與 doxorubicin 對乳癌細胞有加成的抑制效果。綜合這些實驗的結果，本研究提出了幾種 1,4-benzodiazepine-2,5-dione 衍生物，具有抗腫瘤治療的發展潛力。 Benzodiazepinedione is a basic structure for development of drugs, however, little is known about the anti-cancer activity of a benzodiazepinedione compound family. In this study, I synthesized some 1,4-benzodiazepine-2,5-dione derivatives and tested their anti-tumor activity. The results showed that five 1,4-benzodiazepine-2,5-dione derivatives had significantly inhibitory effect on fibroblast-mediated breast tumorigenesis of MDA-MB-468 cells by soft agar colony formation assay. The cell viability assay showed that the chloric and bromic 1,4-benzodiazepine-2,5-dione derivatives decreased survival of breast cancer MDA-MB-468 cells, however, they also exhibited toxic to fibroblasts and non-cancer epithelial M10 cells. Two methylated 1,4-benzodiazepine-2,5-dione derivatives decreased breast cancer’s viability whereas they showed little inhibitory effect on fibroblasts and M10 cells. In addition, combination of 1,4-benzodiazepine-2,5-dione and doxorubicin had additional inhibitory effect on breast cancer cells. Here, we showed some 1,4-benzodiazepine-2,5-dione derivatives may be a good candidate for anti-tumor therapeutics.
作者:	吳承芳
貢獻者:	生物科技系田孝威
關鍵字:	纖維母細胞乳癌 benzodiazepinedione fibroblast breast cancer benzodiazepinedione
日期:	2020
上傳時間:	2022-10-21 10:26:46 (UTC+8)
關聯:	電子全文公開日期：2023-01-08 學年度：108， 52頁
顯示於類別:	[生物科技系(所)] 博碩士論文

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