Validation of Polo-like kinase 1 as a therapeutic target in pancreatic cancer cells
Validation of Polo-like kinase 1 as a therapeutic target in pancreatic cancer cells
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验证 Polo 样激酶 1 作为胰腺癌细胞治疗靶点
DOI：
10.4161/cbt.21412
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发表时间：
2012-10-01
影响因子：
3.6
通讯作者：
Li, Dengwen
中科院分区：
文献类型：
--
作者：
Zhang, Chao;Sun, Xiaodong;Li, Dengwen
Polo样激酶1（PLK 1）是一种丝氨酸/苏氨酸蛋白激酶，在有丝分裂中起着关键作用。PLK 1也被认为是癌症治疗的一个有价值的靶点，几种PLK 1抑制剂目前正在进行临床研究。在这项研究中，我们的数据表明，PLK 1的表达水平在人胰腺癌细胞中上调。分子模拟研究表明，DMTC通过竞争性取代其结合口袋中的ATP来抑制PLK 1活性。我们的数据进一步表明，DMTC抑制胰腺癌细胞的增殖，并诱导多核细胞的形成，最终导致凋亡。此外，联合指数分析表明，DMTC与化疗药物吉西他滨在抑制胰腺癌细胞增殖方面具有协同作用。因此，这些结果表明使用PLK 1抑制剂治疗胰腺癌的潜力。
Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase and plays a critical role in mitosis. PLK1 has also been regarded as a valuable target for cancer treatment, and several PLK1 inhibitors are currently undergoing clinical investigations. In this study, our data show that the expression level of PLK1 is upregulated in human pancreatic cancer cells. Molecular modeling studies indicate that DMTC inhibits PLK1 activity through competitive displacement of ATP from its binding pocket. Our data further show that DMTC suppresses the proliferation of pancreatic cancer cells and induces the formation of multinucleated cells, ultimately resulting in apoptosis. In addition, combination index analysis demonstrates that DMTC acts synergistically with the chemotherapeutic drug gemcitabine in inhibiting the proliferation of pancreatic cancer cells. These results thus suggest a potential of using PLK1 inhibitors for the treatment of pancreatic cancer.