Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China.
Oxid Med Cell Longev. 2021 Mar 3;2021:6633867. doi: 10.1155/2021/6633867. eCollection 2021.
Acquired resistance occurred in the majority of nonsmall cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy, and this may be related to the activation of the HIF-1 pathway. Therefore, we examined the influence of the hypoxia-inducible factor-1 (HIF-1) pathway inhibition on the sensitivity of HCC827 gefitinib-resistant (HCC827 GR) cells with MET amplification to gefitinib.
We established HCC827 GR cell line with MET amplification and set four groups with different treatment. An MTT assay, a colony formation analysis, and a wound healing assay were performed to determine the sensitivity change of HCC827 GR cells after different treatments. HIF-1, p-EGFR, and p-Met levels were detected with western blot. Correlations among HIF-1, p-EGFR, and p-Met levels of HCC827 GR cells with different treatments were analyzed with Pearson's correlation analysis.
HIF-1 inhibitor YC-1 enhanced the sensitivity of HCC827 GR cells to gefitinib. p-Met level was correlated with HIF-1 level, while there was no correlation between p-Met level and p-EGFR level.
HIF-1 inhibitor YC-1 is able to reverse the acquired resistance of HCC827 GR to gefitinib, and the regulation of the HIF-1 pathway on MET may be one of the mechanisms.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗后，大多数非小细胞肺癌（NSCLC）患者出现获得性耐药，这可能与 HIF-1 通路的激活有关。因此，我们研究了缺氧诱导因子-1（HIF-1）通路抑制对 MET 扩增的 HCC827 吉非替尼耐药（HCC827 GR）细胞对吉非替尼敏感性的影响。
我们建立了 MET 扩增的 HCC827 GR 细胞系，并设置了四组不同的处理组。采用 MTT 检测、集落形成分析和划痕愈合实验来确定 HCC827 GR 细胞在不同处理后的敏感性变化。采用 Western blot 检测 HIF-1、p-EGFR 和 p-Met 水平。采用 Pearson 相关分析分析不同处理组 HCC827 GR 细胞中 HIF-1、p-EGFR 和 p-Met 水平之间的相关性。
HIF-1 抑制剂 YC-1 增强了 HCC827 GR 细胞对吉非替尼的敏感性。p-Met 水平与 HIF-1 水平相关，而 p-Met 水平与 p-EGFR 水平之间无相关性。
HIF-1 抑制剂 YC-1 能够逆转 HCC827 GR 对吉非替尼的获得性耐药，HIF-1 通路对 MET 的调节可能是其中的机制之一。
