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Hypoxia Inducible Factor-1α Inhibition in Von Hippel Lindau-mutant Malignant Pleural Mesothelioma Cells.

缺氧诱导因子-1α 对Von Hippel Lindau突变型恶性胸膜间皮瘤细胞的抑制作用。

  • 影响因子:1.90
  • DOI:10.21873/anticanres.14140
  • 作者列表:"Shukuya T","Oyanagi J","Serizawa M","Watanabe M","Yamamoto N","Koh Y
  • 发表时间:2020-04-01
Abstract

BACKGROUND/AIM:Molecular targeted agents have been successfully developed against solid tumors and their use is also being investigated for the treatment of malignant pleural mesothelioma (MPM). We have previously reported von Hippel Lindau (VHL) mutations detected by massive parallel sequencing technology in samples of patients with MPM. Here, we conducted an in vitro study to investigate the therapeutic approaches in VHL-mutant MPM. MATERIALS AND METHODS:Three MPM cell lines with or without a VHL mutation were used and the effects of molecular-targeted agents on growth inhibition were evaluated. Based on the characteristics of the molecular targeted agents that exhibited growth inhibitory effect, the effects of knockdown by siRNA were also evaluated. RESULTS:NCI-H28 MPM cells harboring the VHL L89H mutation were sensitive to YC-1, known as an inhibitor of hypoxia inducible factor (HIF)-1α, and YC-1treatment induced massive apoptosis in a dose-and-time-dependent manner. Knockdown of HIF-1α by siRNA partially inhibited the growth of NCI-H28 cells, suggesting that an additional blockade may be required to completely inhibit growth signaling. CONCLUSION:The VHL mutation may predict tumor responses to YC-1, a HIF-1α inhibitor.

摘要

背景/目的: 已经成功地开发了针对实体瘤的分子靶向剂,并且还正在研究其用于治疗恶性胸膜间皮瘤 (MPM) 的用途。我们之前已经报道了通过大规模平行测序技术在MPM患者样本中检测到的von Hippel Lindau (VHL) 突变。在这里,我们进行了一项体外研究,以研究VHL突变MPM的治疗方法。 材料和方法: 使用三种具有或不具有VHL突变的MPM细胞系,并评估分子靶向剂对生长抑制的作用。基于显示生长抑制作用的分子靶向剂的特征,还评价了siRNA的敲低作用的效果。 结果: NCI-H28 个携带VHL L89H突变的MPM细胞对YC-1 敏感,称为缺氧诱导因子 (HIF)-1α 抑制剂,和YC-1treatment以剂量和时间依赖的方式诱导大量凋亡。SiRNA对HIF-1α 的敲低部分抑制了NCI-H28 细胞的生长,表明可能需要额外的阻断以完全抑制生长信号传导。 结论: VHL突变可预测肿瘤对HIF-1α 抑制剂YC-1 的反应。

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影响因子:6.93
发表时间:2020-01-15
DOI:10.1002/ijc.32532
作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

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影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32530
作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

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肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

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