Taxol and anti-stathmin therapy: a synergistic combination that targets the mitotic spindle.
Taxol and anti-stathmin therapy: a synergistic combination that targets the mitotic spindle.
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发表时间：
2000-07
期刊：
影响因子：
11.2
通讯作者：
C. Iancu;S. Mistry;S. Arkin;G. Atweh
中科院分区：
文献类型：
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作者：
C. Iancu;S. Mistry;S. Arkin;G. Atweh
Stathmin 是一种丰富的胞质磷蛋白，在细胞增殖的调节中发挥重要作用。其主要功能是促进构成有丝分裂纺锤体的微管解聚。紫杉醇是一种有效的化疗剂，其活性是通过稳定有丝分裂纺锤体的微管来介导的。我们证明，stathmin 表达的反义抑制使 K562 白血病细胞对紫杉醇的抗肿瘤作用产生化学敏感性，并导致其生长和克隆形成潜力的协同抑制。在存在 Stathmin 抑制作用的情况下，接触紫杉醇会导致更严重的有丝分裂异常（亚二倍体和多核）。这反过来又导致随后的细胞分裂周期中非整倍体细胞的凋亡增加。这种新颖的基于分子的治疗方法可能提供一种有效的癌症治疗形式，避免与使用具有重叠毒性特征的多种化疗药物相关的严重毒性。
Stathmin is an abundant cytosolic phosphoprotein that plays an important role in the regulation of cellular proliferation. Its major function is to promote depolymerization of the microtubules that make up the mitotic spindle. Taxol is an effective chemotherapeutic agent whose activity is mediated through stabilization of the microtubules of the mitotic spindle. We demonstrate that antisense inhibition of stathmin expression chemosensitizes K562 leukemic cells to the antitumor effects of Taxol and results in a synergistic inhibition of their growth and clonogenic potential. In the presence of stathmin inhibition, exposure to Taxol results in more severe mitotic abnormalities (hypodiploidy and multinucleation). This, in turn, results in increased apoptosis of the aneuploid cells during subsequent cell division cycles. This novel molecular-based therapeutic approach may provide an effective form of cancer therapy that would avoid the severe toxicities associated with the use of multiple chemotherapeutic agents with overlapping toxicity profiles.