泰莫西芬與BP012W乙醇分離物之協同作用造成強化管狀A型乳腺癌細胞凋亡影響;Synergy effects of tamoxifen and the ethanol fractions of BP012W to enhance apoptosis of luminal-A breast cancer cells

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题名:	泰莫西芬與BP012W乙醇分離物之協同作用造成強化管狀A型乳腺癌細胞凋亡影響;Synergy effects of tamoxifen and the ethanol fractions of BP012W to enhance apoptosis of luminal-A breast cancer cells
作者:	鄧棨文;Deng,Chi-Wen
贡献者:	系統生物與生物資訊研究所
关键词:	乳癌;中草藥;泰莫西芬;合併治療;Breast cancer;Traditional Chinese Medicines;Tamoxifen;Synergistic anticancer effects
日期:	2016-07-27
上传时间:	2016-10-13 13:24:47 (UTC+8)
出版者:	國立中央大學
摘要:	乳癌一直是女性死亡的主要原因，而且死亡人數也是逐年上升。目前最為廣泛使用的化癌藥物，泰莫西芬，作為乳癌的賀爾蒙治療藥物，但若是長期使用容易衍生抗藥性。雖然泰莫西芬效果好，但也會造成像是子宮頸癌和血管栓塞的不良副作用。在中國，傳統中草藥早已用在治療癌症許多年了，其特性相較於化癌藥物，除了毒性較低，也比較少衍生出不好的副作用。本文利用高通量細胞學藥物篩選系統，從60種此類中草藥篩選出蒲公英的萃取物BP012W，BP012W對於管狀A型乳癌細胞株MCF-7表現很強的抑制生長的效果，因此本文我們選擇BP012W做更深入的研究。我們接著用西方墨點法，發現管狀A行乳癌細胞株MCF-7的BAX蛋白質表現量隨著藥物治療而上升，同時Bcl-2的蛋白質表現量則隨之下降。最後我們利用玻璃管柱層析法，將BP012W做藥物分層，依據乙醇濃度變化，0%、20%、40%、60%、80% 和99.9%，並發現只有0% 和20% 仍保持原藥物抑制生長的特性，因此我們將0% 和20% 做合併為EP1，確實發現EP1疊加了0% 和20% 的效果表現最好，最後我們用泰莫西芬做合併治療，發現在管狀A型乳癌細胞株MCF-7，EP1的合併效果比BP012W的合併效果來的好。BP012W和其分成翠取的EP1可能是一個有希望的候選藥物作為乳腺癌治療化療上。 ;Breast cancer has been ranked the first leading cause of death among female, and the numbers have been rising over the years. Tamoxifen is the most widely used anti-estrogen for the treatment of breast cancer, but resistance often develops due to long-term use. In addition, adverse side effects including uterine cancer and thromboembolic disease have been attributed to the use of tamoxifen. Traditional Chinese Medicines (TCMs) have been applied for the treatment of cancer in China for many years due to low toxicity and side effects. In this study, we screened 60 TCMs and found that BP012W, one of the families of Asteraceae, showed strong growth inhibition toward luminal-A breast cancer cell line MCF-7, thus was chosen for further studies. The western blot analysis indicated that BAX proteins were increased in expression while BCL-2 was decreased in expression. The DIAION column extraction was performed for isolation of pure compounds from BP012W using different concentrations of ethanol, 0%, 20%, 40%, 60%, 80% and 99.9%, and found that the concentrations at 0% and 20% were most effective in inhibiting proliferation of cells than the crude extract and was denoted EP1. Furthermore, BP012W showed stronger growth inhibition of MCF-7 cells when in combination with tamoxifen than applying tamoxifen alone. BP012W may be a promising candidate as a chemosensitizer for breast cancer treatments.
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