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| 不可逆性泛HER抑制剂HM781-36B在埃罗替尼耐药型非小细胞肺癌中的抗肿瘤活性 |
| Antitumor activity of HM781-36B, an irreversible pan-HER inhibitor in erlotinib-resistant NSCLC |
| 投稿时间：2016-01-22 |
| DOI：10.3969/j.issn.1000-0399.2017.01.008 |
| 中文关键词: HM781-36B 泛人表皮生长因子受体抑制剂 埃罗替尼,耐药 非小细胞肺癌 |
| 英文关键词: HM781-36B Pan-HER inhibitor Erlotinib,resistance Non-small cell lung cancer |
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| 中文摘要: |
| 目的 研究不可逆性泛人表皮生长因子受体（HER）抑制剂HM781-36B对埃罗替尼耐药型非小细胞肺癌细胞株NCI-H1975的体外抗肿瘤活性。方法 采用水溶性甲臢化合物（MTS）法检测HM781-36B抑制NCI-H1975细胞的体外增殖能力；利用流式细胞检测技术探讨其可能的作用机制；Western blot检测HM781-36B对HER家族（pEGFR和pHER2）和下游TEC通路（pERK和pAKT）的抑制作用。结果 HM781-36B（0.001~10 μM）能够剂量依赖性地抑制NCI-H1975细胞的体外增殖；HM781-36B处理NCI-H1975细胞后，诱导其细胞凋亡和G1细胞周期停滞；并抑制HER家族（pEGFR和pHER2）的表达和阻止下游信号级联放大的关键成分（pERK和pAKT）。结论 HM781-36B可能成为治疗第一代EGFR-TKI耐药非小细胞肺癌的有效药物。 |
| 英文摘要: |
| Objective To evaluate the antitumor activity and mechanism of action for HM781-36B, a novel and irreversible pan-human epidermal growth factor receptor (HER) inhibitor, in NCI-H1975 cells. Methods Cell growth inhibition assay was examined by MTS, the change in the cell cycle was determined by flow cytometry, and the protein expression of HER family (pEGFR and pHER2) and downstream signaling molecules(pERK and pAKT, member of the TEC family nonreceptor/cytoplasmic tyrosine kinases) was detected by Western blot. Results The addition of HM781-36B(0.001~10 μM) induced potent growth inhibition in NCI-H1975 cells in a dose-dependent manner. Furthermore, HM781-36B induced apoptosis and G1 arrest of the cell cycle and reduced the levels of HER family (pEGFR and pHER2) and downstream signaling molecules(pERK and pAKT). Conclusion These findings suggest that HM781-36B will be advantageous for the treatment of NSCLC patients with the first generation of EGFR-TKI clinical resistance. |
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