Combining miR-10b-Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer.
Combining miR-10b-Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer.
复制标题
将miR-10b靶向的纳米疗法与低剂量阿霉素结合起来，引起转移性乳腺癌的持久回归。
DOI：
10.1158/0008-5472.can-15-0888
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发表时间：
2015-10-15
期刊：
影响因子：
11.2
通讯作者：
Medarova Z
中科院分区：
文献类型：
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作者：
Yoo B;Kavishwar A;Ross A;Wang P;Tabassum DP;Polyak K;Barteneva N;Petkova V;Pantazopoulos P;Tena A;Moore A;Medarova Z
微小RNA在癌症中的治疗前景尚未实现。在这项研究中，我们确定并在治疗上开发了miR-10b在转移部位的一个新角色，它将其过度表达与肿瘤细胞的生存和增殖联系起来。在开发的方案中，我们将miR-10b抑制纳米片与低剂量蒽环类药物相结合，在转移性乳腺癌的小鼠模型中实现了转移性疾病的完全持久消退。机械学研究表明，纳米片在转移细胞中具有强大的抗增殖、促凋亡作用，并因给予低剂量的蒽环类药物而导致细胞周期停滞而增强。MiR-10b在具有高转移潜能的细胞中特异地过度表达，表明该miRNA作为转移特异性治疗靶点的作用。综上所述，我们的结果暗示，只有在肿瘤细胞获得在远处转移部位生长的能力后，才存在调节肿瘤细胞活力和增殖的途径。如miR-10b靶向所示，这种依赖于转移的凋亡通路将为进一步的治疗探索提供有吸引力的靶点。
The therapeutic promise of microRNA in cancer has yet to be realized. In this study, we identified and therapeutically exploited a new role for miR-10b at the metastatic site, which links its overexpression to tumor cell viability and proliferation. In the protocol developed, we combined a miR-10b-inhibitory nanodrug with low-dose anthracycline to achieve complete durable regressions of metastatic disease in a murine model of metastatic breast cancer. Mechanistic investigations suggested a potent anti-proliferative, pro-apoptotic effect of the nanodrug in the metastatic cells, potentiated by a cell-cycle arrest produced by administration of the low-dose anthracycline. miR-10b was overexpressed specifically in cells with high metastatic potential, suggesting a role for this miRNA as a metastasis-specific therapeutic target. Taken together, our results implied the existence of pathways that regulate the viability and proliferation of tumor cells only after they have acquired the ability to grow at distant metastatic sites. As illustrated by miR-10b targeting, such metastasis-dependent apoptotic pathways would offer attractive targets for further therapeutic exploration.