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題名 | 薑黃素藉由抑制NF-κB的活性增強對放射線毒殺乳癌細胞MCF-7之毒殺效果=Curcumin Enhances Radiation-Induced Cytotoxicity Via Suppression of NF-κB Activation in Breast Cancer MCF-7 Cells |
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作者 | 柳光欣; 王守正; 許錦龍; 莊曜禎; 李意旻; 林松水; | 書刊名 | 中華放射線技術學雜誌 |
卷期 | 38:1 2014.03[民103.03] |
頁次 | 頁1-8 |
分類號 | 416.226 |
關鍵詞 | 薑黃素; 核轉錄因子-kappaB; 乳癌; 細胞凋亡; Curcumin; NF-κB; Breast cancer; Apoptosis; |
語文 | 中文(Chinese) |
中文摘要 | 乳癌是最常好發於世界女性的惡性癌症之一,放射線治療是臨床上乳癌最常用的治療方法之一,但是許多病人在經過放射治療後的結果是不佳的,其原因是因為放射線會誘導腫瘤細胞產生輻射抗性。輻射抗性的表現是因為放射線活化腫瘤的核轉錄因子-kappaB(Nuclear factor-kappaB,NF-κB)的活性,被活化的NF-κB可以正向調節抗凋亡基因的產生,進而抑制放射線的抗癌效果。薑黃素(curcumin)是從鬱金根部所萃取出的多酚類成分,是著名的天然NF-κB抑制劑,本研究主要是探討薑黃素增進乳癌細胞對放射線的敏感度,是否與薑黃素抑制放射線誘導NF-κB的活性有關。本研究應用群落形成試驗評估薑黃素結合放射線對人類乳癌細胞株-MCF-7細胞的生長影響,利用去氧核醣核酸片段試驗分析薑黃素是否會促進放射線誘導MCF-7細胞的凋亡,並運用西方墨點法確認薑黃素對放射線活化NF-κB及其所調控的抗凋亡蛋白的影響。研究結果顯示薑黃素可以顯著地增加放射線對MCF-7細胞的生長抑制,薑黃素可藉由增加MCF-7的粒線體和非粒線體的凋亡路徑,強化放射線誘導細胞凋亡的發生。西方墨點法的結果顯示:薑黃素會減少放射線活化MCF-7細胞內的NF-κB活性和受NF-κB所調控的抗凋亡蛋白Bcl-2和C-FLIP等的表現,進一步因NF-κB的活性受到抑制會造成MCF-7細胞對放射線變得更敏感,證實薑黃素是乳癌細胞株的輻射敏感劑。 |
英文摘要 | Breast cancer is the most common malignancy in women around the world. Radiotherapy is one of the treatment modality used in multidisciplinary strategy against breast cancer nowadays. Recurrence after radiotherapy is not uncommon and it may be resulted from induced radioresistance. Radiation-induced NF-κB activity can upregulate anti-apoptotic genes in irradiated breast cancer cells. Curcumin is plant phytochemical derived from the root of Curcuma longa and known for the inhibitory effect on NF-κB activity. The main goal of this study is to investigate whether curcumin is able to radiosensitize breast cancer cells through suppression of radiation-induced NF-κB activity. In this study, the effects of curcumin combined with radiation on cell proliferation in MCF-7 cells were evaluated with clonogenic formation assay. Whether curcumin can increase radiation-induced apoptosis was investigated by using DNA fragmentation assay. We also determined the effects of curcumin on radiation-induced NF-κB activity and increased the expression of NF-κB regulated gene products with Western blotting assay. To confirm whether NF-κB inhibition can sensitize breast cancer to radiation, the effects of NF-κB inhibitor combined with radiation in MCF-7 cell were evaluated in this study. These results showed that curcumin can significantly increase radiation-inhibited cell proliferation as compared to radiation alone. Curcumin also enhanced radiation-induced cell apoptosis via dependent and independent mitochondrial pathways. We also found curcumin decreased radiation activated NF-κB activity and increased the expression of NF-κB regulated gene products (Bcl-2 and C-FLIP) from Western blotting assay. In addition, the results also showed NF-κB inhibitor can increase radiosensitivity in MCF-7 cell. |
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