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購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物 www.pyjb.com.cn |
最專業(yè)有效的細胞離心涂片系統(tǒng) Tharmac® Cellspin 載玻片離心機 (點擊標題進入) 細胞治療所使用的無血清培養(yǎng)基 lonza 04-418Q 無血清培養(yǎng)基 (點擊標題進入) 干細胞治療所使用的無血清培養(yǎng)基lonza 12-725F 無血清培養(yǎng)基 (點擊標題進入)
近日,國際生物學(xué)期刊cell death &differentiation發(fā)表了來自加拿大和中國科學(xué)家的一項最近研究成果。研究人員通過體內(nèi)和體外實驗證明激活toll-like receptor 3(TLR3)能夠促進乳腺癌細胞向腫瘤干細胞(CSC)轉(zhuǎn)化,產(chǎn)生干細胞特征,而TLR3的這種促CSC轉(zhuǎn)化效應(yīng)需要同時激活β catenin和NF-κB信號通路才能發(fā)生。這一研究成果為癌癥治療中抑制CSC產(chǎn)生提供了新的策略。 研究人員指出,在2012年的統(tǒng)計中,乳腺癌是導(dǎo)致女性死亡的第二大疾病。傳統(tǒng)療法如放療和化療能夠消除腫瘤腫塊,但對少數(shù)具有惡性作用的腫瘤細胞仍然不能起到完全殺死的作用,這些惡性腫瘤細胞仍然能夠存活并自我更新,進一步發(fā)展為惡性腫瘤,這一類細胞就叫做腫瘤干細胞。研究發(fā)現(xiàn),腫瘤干細胞對傳統(tǒng)療法具有抵抗作用,并且能夠在某些條件下由非腫瘤干細胞轉(zhuǎn)化而來。而TLR3在不良預(yù)后的乳腺癌病人中具有更高的表達,但TLR3與乳腺癌細胞向腫瘤干細胞轉(zhuǎn)化之間的關(guān)系仍然不清楚。 研究人員首先通過體外細胞培養(yǎng)發(fā)現(xiàn),激活TLR3能夠促進乳腺癌細胞產(chǎn)生類似腫瘤干細胞的特征,但TLR5,7,8并不能起到相同作用。通過對機制進一步探討,單獨激活NF-κB信號通路并不能引起乳腺癌細胞向腫瘤干細胞的轉(zhuǎn)化,而當同時激活β catenin和NF-κB信號同路時,才能夠促進TLR3介導(dǎo)的乳腺癌細胞向腫瘤干細胞的轉(zhuǎn)化。研究人員還發(fā)現(xiàn),利用小豆蔻明處理乳腺癌細胞能夠阻斷β catenin和NF-κB信號通路,導(dǎo)致TLR3介導(dǎo)的CSC轉(zhuǎn)化過程受到抑制。 綜上所述,該項研究發(fā)現(xiàn)TLR3能夠同時激活β catenin和NF-κB信號通路,促進乳腺癌細胞向腫瘤干細胞轉(zhuǎn)化,并且發(fā)現(xiàn)小豆蔻明能夠阻斷TLR3的這種作用,抑制腫瘤細胞向腫瘤干細胞的轉(zhuǎn)化。這一研究成果為抑制CSC產(chǎn)生,提高癌癥治愈率提供了新的策略。 原文標題:β -Catenin and NF-κB co-activation triggered by TLR3 stimulation facilitates stem Cell-like phenotypes in breast cancer Cancer stem cells (CSCs) are responsible for tumor initiation and progression. Toll-like receptors (TLRs) are highly expressed in cancer cells and associated with poor prognosis. However, a linkage between CSCs and TLRs is unclear, and potential intervention strategies to prevent TLR stimulation-induced CSC formation and underlying mechanisms are lacking. Here, we demonstrate that stimulation of toll-like receptor 3 (TLR3) promotes breast cancer cells toward a CSC phenotype in vitro and in vivo. Importantly, conventional NF-κB signaling pathway is not exclusively responsible for TLR3 activation-enriched CSCs. Intriguingly, simultaneous activation of both β-catenin and NF-κB signaling pathways, but neither alone, is required for the enhanced CSC phenotypes. We have further identified a small molecule cardamonin that can concurrently inhibit β-catenin and NF-κB signals. Cardamonin is capable of effectively abolishing TLR3 activation-enhanced CSC phenotypes in vitro and successfully controlling TLR3 stimulation-induced tumor growth in human breast cancer xenografts. These findings may provide a foundation for developing new strategies to prevent the induction of CSCs during cancer therapies. |
購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物
www.pyjb.com.cn |
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