Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells.
Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells.
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FDA 批准的驱虫药氟苯达唑针对乳腺癌干细胞样细胞
DOI：
10.18632/oncotarget.3436
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发表时间：
2015-03-20
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Hou ZJ;Luo X;Zhang W;Peng F;Cui B;Wu SJ;Zheng FM;Xu J;Xu LZ;Long ZJ;Wang XT;Li GH;Wan XY;Yang YL;Liu Q
Cancer stem-like cell （CS-like cell）被认为是乳腺癌复发和耐药事件的主要原因，这使其成为新的癌症治疗策略的潜在靶点。经FDA批准的氟苯达唑，已被广泛用于治疗肠道寄生虫。在这里，我们证明了氟苯达唑对乳腺cs样细胞的新作用。氟苯达唑通过腹腔注射抑制乳腺癌细胞增殖呈剂量和时间依赖性，并延缓异种移植瘤模型的肿瘤生长。重要的是，氟苯达唑降低了cd44高/ cd24低亚群，抑制了乳腺球的形成和自我更新相关基因的表达，包括c-myc、oct4、sox2、nanog和cyclinD1。此外，我们发现氟苯达唑诱导细胞分化并抑制细胞迁移。氟苯达唑降低了乳腺癌细胞间充质标志物（β-catenin、N-cadherin和Vimentin）的表达，并诱导了上皮和分化标志物（角蛋白18）的表达。机制研究表明，氟苯达唑通过抑制微管蛋白聚合，使细胞周期停留在G2/M期，诱导单极纺锤体形成。此外，氟苯达唑增强了传统治疗药物氟尿嘧啶和阿霉素对乳腺癌细胞的细胞毒活性。总之，我们的研究结果揭示了氟苯达唑对乳腺cs样细胞的显著抑制作用，表明氟苯达唑在乳腺癌治疗中的新应用。
Cancer stem-like cell (CS-like cell) is considered to be responsible for recurrence and drug resistance events in breast cancer, which makes it a potential target for novel cancer therapeutic strategy. The FDA approved flubendazole, has been widely used in the treatment of intestinal parasites. Here, we demonstrated a novel effect of flubendazole on breast CS-like cells. Flubendazole inhibited breast cancer cells proliferation in dose- and time-dependent manner and delayed tumor growth in xenograft models by intraperitoneal injection. Importantly, flubendazole reduced CD44high/CD24low subpopulation and suppressed the formation of mammosphere and the expression of self-renewal related genes including c-myc, oct4, sox2, nanog and cyclinD1. Moreover, we found that flubendazole induced cell differentiation and inhibited cell migration. Consistently, flubendazole reduced mesenchymal markers (β-catenin, N-cadherin and Vimentin) expression and induced epithelial and differentiation marker (Keratin 18) expression in breast cancer cells. Mechanism study revealed that flubendazole arrested cell cycle at G2/M phase and induced monopolar spindle formation through inhibiting tubulin polymerization. Furthermore, flubendazole enhanced cytotoxic activity of conventional therapeutic drugs fluorouracil and doxorubicin against breast cancer cells. In conclusion, our findings uncovered a remarkable effect of flubendazole on suppressing breast CS-like cells, indicating a novel utilization of flubendazole in breast cancer therapy.
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影响因子：
--
作者：
Hayashida T;Jinno H;Kitagawa Y;Kitajima M
通讯作者：
Kitajima M
影响因子：
45.3
作者：
Jiralerspong, Sao;Palla, Shana L.;Gonzalez-Angulo, Ana M.
通讯作者：
Gonzalez-Angulo, Ana M.
影响因子：
45.3
作者：
Gianni, Luca;Baselga, Jose;Bonadonna, Gianni
通讯作者：
Bonadonna, Gianni
影响因子：
5.7
作者：
Ding, Wei-Qun;Liu, Bolin;Lind, Stuart E.
通讯作者：
Lind, Stuart E.
影响因子：
168.9
作者：
Albain, K.;Anderson, S.;Arriagada, R.;Barlow, W.;Bergh, J.;Bliss, J.;Buyse, M.;Cameron, D.;Carrasco, E.;Clarke, M.;Correa, C.;Coates, A.;Collins, R.;Costantino, J.;Cutter, D.;Cuzick, J.;Darby, S.;Davidson, N.;Davies, C.;Davies, K.;Delmestri, A.;Di Leo, A.;Dowsett, M.;Elphinstone, P.;Evans, V.;Ewertz, M.;Gelber, R.;Gettins, L.;Geyer, C.;Goldhirsch, A.;Godwin, J.;Gray, R.;Gregory, C.;Hayes, D.;Hill, C.;Ingle, J.;Jakesz, R.;James, S.;Kaufmann, M.;Kerr, A.;MacKinnon, E.;McGale, P.;McHugh, T.;Norton, L.;Ohashi, Y.;Paik, S.;Pan, H. C.;Perez, E.;Peto, R.;Piccart, M.;Pierce, L.;Pritchard, K.;Pruneri, G.;Raina, V.;Ravdin, P.;Robertson, J.;Rutgers, E.;Shao, Y. F.;Swain, S.;Taylor, C.;Valagussa, P.;Viale, G.;Whelan, T.;Winer, E.;Wang, Y.;Wood, W.
通讯作者：
Wood, W.