A marine anthraquinone SZ-685C overrides adriamycin-resistance in breast cancer cells through suppressing Akt signaling.
A marine anthraquinone SZ-685C overrides adriamycin-resistance in breast cancer cells through suppressing Akt signaling.
复制标题
海洋蒽醌 SZ-685C 通过抑制 Akt 信号传导来克服乳腺癌细胞对阿霉素的耐药性
作者：
Zhu X;He Z;Wu J;Yuan J;Wen W;Hu Y;Jiang Y;Lin C;Zhang Q;Lin M;Zhang H;Yang W;Chen H;Zhong L;She Z;Chen S;Lin Y;Li M
乳腺癌仍然是世界范围内的一个主要健康问题。虽然化疗是治疗乳腺癌的一种重要方法，但由于化疗耐药性，化疗的临床应用仍然存在巨大的局限性。HER2/PI-3K/Akt通路已被证明在乳腺癌细胞产生广泛的化疗耐药中起因果作用，因此被证明是增强阿霉素(ADR)等抗乳腺癌化疗效果的靶点。乳腺癌的治疗迫切需要既能增强化疗效果又能克服化疗耐药的药物。在这种情况下，SZ-685C，一种先前已被证明抑制Akt信号转导的药物，有望增加化疗的疗效。我们目前的研究探讨了SZ-685C是否可以通过抑制Akt信号通路来逆转人乳腺癌细胞的化疗耐药。以人乳腺癌细胞株MCF-7、MCF-7/ADR和MCF-7/Akt耐药细胞为模型，检测SZ-685C的作用。我们发现SZ-685C抑制Akt通路，诱导ADR耐药的MCF-7/ADR和MCF-7/Akt细胞凋亡，从而在体内外发挥抗肿瘤作用。我们的数据表明，使用SZ-685C可能是治疗耐药乳腺癌的一种潜在的有前途的方法。
Breast cancer remains a major health problem worldwide. While chemotherapy represents an important therapeutic modality against breast cancer, limitations in the clinical use of chemotherapy remain formidable because of chemoresistance. The HER2/PI-3K/Akt pathway has been demonstrated to play a causal role in conferring a broad chemoresistance in breast cancer cells and thus justified to be a target for enhancing the effects of anti-breast cancer chemotherapies, such as adriamycin (ADR). Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance are urgently needed for the treatment of breast cancer. In this context, SZ-685C, an agent that has been previously shown, as such, to suppress Akt signaling, is expected to increase the efficacy of chemotherapy. Our current study investigated whether SZ-685C can override chemoresistance through inhibiting Akt signaling in human breast cancer cells. ADR-resistant cells derived from human breast cancer cell lines MCF-7, MCF-7/ADR and MCF-7/Akt, were used as models to test the effects of SZ-685C. We found that SZ-685C suppressed the Akt pathway and induced apoptosis in MCF-7/ADR and MCF-7/Akt cells that are resistant to ADR treatment, leading to antitumor effects both in vitro and in vivo. Our data suggest that use of SZ-685C might represent a potentially promising approach to the treatment of ADR-resistant breast cancer.
登录
查看更多内容
影响因子：
8
作者：
Knuefermann, C;Lu, Y;Fan, Z
通讯作者：
Fan, Z
影响因子：
3.9
作者：
Knight, Z. A.;Shokat, K. M.
通讯作者：
Shokat, K. M.
影响因子：
3.7
作者：
Zhang, Weijia;Ding, Wei;He, Zhimin
通讯作者：
He, Zhimin
SZ-685C 是一种海洋蒽醌，是一种有效的细胞凋亡诱导剂，通过抑制 Akt/FOXO 途径具有抗癌活性
影响因子：
7.3
作者：
Xie, Gui'e;Zhu, Xun;Yuan, Jie
通讯作者：
Yuan, Jie
影响因子：
--
作者：
VICKERS, PJ;DICKSON, RB;COWAN, KH
通讯作者：
COWAN, KH