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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >A Small-molecule Kinase Inhibitor, CEP-1347, Inhibits Survivin Expression and Sensitizes Ovarian Cancer Stem Cells to Paclitaxel
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A Small-molecule Kinase Inhibitor, CEP-1347, Inhibits Survivin Expression and Sensitizes Ovarian Cancer Stem Cells to Paclitaxel

机译：小分子激酶抑制剂Cep-1347抑制存活素的表达，并敏感卵巢癌干细胞对紫杉醇

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Background: Chemoresistance of cancer stem cells (CSCs) is considered a major cause of post-treatment recurrence that negatively impacts the prognosis of patients with ovarian cancer. Materials and Methods: Using CSCs derived from two different ovarian cancer cell lines, we searched for molecules implicated in the chemoresistance of ovarian CSCs and also drugs with which to target those molecules. Results: Knockdown of survivin overexpressed in ovarian CSCs resulted in increased sensitivity to paclitaxel. Treatment at clinically relevant concentrations with CEP-1347, a mixed lineage kinase inhibitor with a known safety profile in humans, reduced survivin expression in ovarian CSCs and sensitized them to paclitaxel. Conclusion: Survivin overexpression plays a key role in the chemoresistance of ovarian CSCs. Introduction of CEP1347, which targets survivin expression in ovarian CSCs, as a chemosensitizer for conventional ovarian cancer chemotherapy may serve as a rational and feasible approach for better management of ovarian cancer.
机译：背景：癌症干细胞（CSC）的化学抑制被认为是治疗后复发的主要原因，对卵巢癌患者的预后产生负面影响。材料和方法：使用来自两种不同卵巢癌细胞系的CSCs，我们搜索了涉及卵巢CSCs的化学抑制的分子，以及其靶向这些分子的药物。结果：在卵巢CSC中过表达的Survivin的敲低导致对紫杉醇的敏感性增加。在临床相关浓度下用CEP-1347治疗，一种具有已知的人类安全性曲线的混合谱系激酶抑制剂，减少了卵巢CSC中的存活蛋白表达并使它们敏化至紫杉醇。结论：Survivin过表达在卵巢CSCs的化学抑制中起着关键作用。诱导卵巢CSC中的Survivin表达的Cep1347引入，作为常规卵巢癌化疗的化学敏化剂，可以作为更好地管理卵巢癌的理性和可行的方法。

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