Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/97752
標題: 去雙甲氧基薑黃素藉由抑制GPR161/mTOR訊息傳遞路徑減少三陰性乳癌增生及轉移能力之研究
Bisdemethoxycurcumin (BDMC) inhibits cell proliferation and metastasis through the suppression of GPR161/mTOR signaling pathway in triple negative breast cancer cells
作者: 呂夢恬
Meng-Tien Lu
關鍵字: 去雙甲氧基薑黃素;三陰性乳癌;G蛋白偶聯受體161;哺乳動物雷帕黴素靶蛋白路徑;Bisdemethoxycurcumin;Triple-negative breast cancer;GPR161;mTOR signaling pathway
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摘要: 
乳癌的分類依細胞受體ER、PR、HER2的過度表現來區分,而三陰性乳癌 (Triple-negative breast cancer ,TNBC) 指的是細胞表面缺乏ER、PR、HER2受體,因此無法使用賀爾蒙治療或是針對HER2進行標靶治療,並且其死亡率較高、預後狀況較差,如何提高三陰性乳癌病患生存率就成為一個十分迫切的問題。先前文獻提到在三陰性乳癌中,使用large-scale genomic analysis,G-protein–coupled receptor, GPR161常會有過度表現的情形,並證實在乳癌中GPR161的過表現會提升乳癌細胞中的增生、爬行以及侵襲能力,且高表現GPR161的乳癌病患存活率也較低。過去對薑黃素的研究中,包含curcumin、bisdemethoxycurcumin (BDMC),demethoxycurcumin (DMC)三種化合物有很好的抗癌活性,若薑黃素能抑制GPR161以及其過度表現所導致的增生轉移情形,就能進一步發展為TNBC的潛在抗癌藥物。本實驗以GPR161表現量較高的三陰性乳癌細胞BT-20進行實驗,發現BDMC在BT20細胞中可抑制GPR161蛋白量以及降低細胞存活率。BDMC能抑制GPR161來減少細胞增生,PARP剪切所造成的細胞凋亡,以及增加細胞黏附蛋白E-cadherin的表現來降低癌細胞的轉移能力,並且透過mTOR抑制劑Rapamycin確認BDMC抑制GPR161然後透過mTOR路徑去抑制三陰性乳癌細胞的增生及轉移能力。
綜合以上結果顯示,BDMC對於GPR161的抑制效果最佳,並且可以透過抑制GPR161減低三陰性乳癌的細胞增生、爬行等侵襲特質,可做為抗癌藥物。

G-protein-coupled receptor 161 (GPR161) is overexpressed specifically in triple-negative breast cancer (TNBC) and correlates with poor prognosis. It is an important regulator and a potential drug target for TNBC.
In the study, we confirmed that GPR161 was overexpressed in TNBC BT-20 cells. Next, we aimed to discover a potential GPR161 inhibitor from natural products, and showed that curcuminoids were more effective than other natural products. Our results revealed that bisdemethoxycurcumin (BDMC) demonstrated the most potent cytotoxic effects on BT-20 cells. Moreover, BDMC inhibited the expression of GPR161 in BT-20 cells. BDMC also demonstrated the most efficient cytotoxic effects on TNBC cells than ER+/PR+ positive breast cancer cells. These results demonstrated that GPR161 plays an important role in TNBC cell viability. Our data also showed that BDMC inhibited the migration and invasion in TNBC cells through the inhibition of MMP9 protein expression and the increase of E-cadherin protein level. Moreover, BDMC induced TNBC cell apoptosis through the activation of caspase 7 and PARP. Interestingly, BDMC inhibited the expression of GPR161 through the suppression of mTOR pathway.
Base on the results show that BDMC has potential of suppresses proliferation and metastasis through the inhibition of GPR161/mTOR signaling pathway in TNBC cells.
URI: http://hdl.handle.net/11455/97752
Rights: 同意授權瀏覽/列印電子全文服務,2021-08-06起公開。
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