Brefeldin A對乳癌細胞MDA-MB-231細胞毒殺作用之研究

The cytotoxicity study of Brefeldin A treatment in MDA-MB-231 human breast cancer cell line

余采蓉(Tsai-Jung Yu)

指導教授 ： 曾昭能

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2012年)

摘要

抗乳癌藥物的研發，已經成為癌症研究的主要方向。越來越多的證據顯示，許多的癌症，包含乳癌，都是由癌症幹細胞所發展而來。本研究應用懸浮培養的方式，建立出對MDA-MB-231的癌症幹細胞之篩選平台，並確認Brefeldin A對癌症幹細胞的專一毒性。結果顯示，懸浮培養時，Brefeldin A會抑制MDA-MB-231的細胞生長，其半致死劑量是0.016 μg/ml。Brefeldin A馬上抑制了MDA-MB-231細胞的遷移與群落形成。利用Annexin V-PI染色法偵測出Brefeldin A處理4小時後，明顯引起MDA-MB-231細胞凋亡。因此，Brefeldin A對人類乳癌細胞顯現出治療潛力。更進一步研究其機轉、效力與安全性是必要的。

關鍵字

癌症幹細胞 ； Salinomycin ； Brefeldin A ； 微球體 ； 群落 ； 細胞群落 ； 早期細胞凋亡

並列摘要

The development of anti-breast cancer drug has become a major direction in cancer research. Accumulating evidence has shown that many types of cancer, including breast cancer, are initiated from and maintained by a small population of cancer stem cells (CSCs). This study applies suspension culture technique to screen agents that target cancer stem cells of MDA-MB-231 cell line and identified Brefeldin A as a cancer stem cell-specific cytotoxic reagent. Results indicated that Brefeldin A treatment inhibited the growth of MDA-MB-231 cells in suspension cultures in a dose-responsive manner (IC50: 0.016 μg/ml). Cell migration and clonogenicity of MDA-MB-231 cells were effectively inhibited by Brefeldin A. Brefeldin A induced apparent apoptosis in MDA-MB-231 cells at 4 hour after treatment as detected by Annexin V-PI staining. Therefore, Brefeldin A has therapeutic potential in treating human breast cancer. Further investigation of the mechanism, effectiveness and safety of Brefeldin A is warranted.

並列關鍵字

CSCs ； Salinomycin ； Brefeldin A ； mammosphere ； colony ； clonogenicity ； early apoptosis

參考文獻

1. Anadu, N. O., V. J. Davisson, et al. (2006). "Synthesis and anticancer activity of brefeldin A ester derivatives." J Med Chem 49(13): 3897-3905.

2. Badve, S. and H. Nakshatri (2012). "Breast-cancer stem cells-beyond semantics." Lancet Oncol 13(1): e43-48.

3. Bhui, K., S. Tyagi, et al. (2012). "Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G(2)/M arrest to apoptosis." Mol Carcinog 51(3): 231-243.

4. Bidinotto, L. T., R. Lopez de Cicco, et al. (2011). "Omega-3 fatty acids: a potential booster for tamoxifen therapy?" Expert Rev Anticancer Ther 11(8): 1151-1153.

5. Buczacki, S., R. J. Davies, et al. (2011). "Stem cells, quiescence and rectal carcinoma: an unexplored relationship and potential therapeutic target." Br J Cancer 105(9): 1253-1259.