...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cancer biology & therapy >In vitro targeting of Polo-like kinase 1 in bladder carcinoma: Comparative effects of four potent inhibitors
【24h】

In vitro targeting of Polo-like kinase 1 in bladder carcinoma: Comparative effects of four potent inhibitors

机译：体外靶向Polo样激酶1在膀胱癌中：四种有效抑制剂的比较作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical tests are still needed to corroborate the usefulness of using them in combination with other commonly used chemotherapeutic drugs.
机译：尽管新辅助化疗有所改善，但在过去30年中，晚期膀胱癌患者的预后几乎没有改变。在本研究中，我们测试并比较了四种不同的Polo样激酶1（PLK1）抑制剂（BI 2536，BI 6727，GW843682X和GSK461364）对3种膀胱癌细胞系RT4、5637和T24的体外抗肿瘤活性。还研究了顺铂，甲氨蝶呤和阿霉素同时治疗对放射敏感性和药物相互作用的影响。我们的结果表明，PLK1抑制可阻止细胞增殖和克隆形成，从而显着抑制肿瘤细胞的侵袭，尽管在药物之间观察到的差异很小。此外，所有PLK1抑制剂均诱导G2 / M阻滞，随后在所有3种细胞系中诱导死亡。药物相互作用研究显示，与常用的顺铂和甲氨蝶呤联用时，所有PLK1抑制剂均获得了吉祥的结果，尽管与阿霉素联用时主要表现出拮抗作用。相比之下，四种PLK1抑制剂有效地使细胞对电离辐射敏感。我们的发现表明，无论使用哪种抑制剂，PLK1的药理抑制作用都会抑制膀胱癌的生长和扩散，为将来的治疗干预提供了新的机会。但是，仍然需要进一步的实验室和临床前测试，以证实将其与其他常用化疗药物联合使用的有效性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号