期刊
ONCOLOGY LETTERS
卷 22, 期 3, 页码 -出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2021.12932
关键词
gefitinib; NSCLC; HIF-1 alpha; angiogenesis; EGFR-TKIs
类别
资金
- National Research Foundation of Korea - Korea government [NRF-2021R1A2C1003297]
- Basic Research Program through the National Research Foundation - Ministry of Science and ICT of Republic of Korea [2019R1F1A1041812]
- National Research Foundation of Korea [2019R1F1A1041812] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The study focused on the dependence of gefitinib resistance on HIF-1 alpha activity, showing that HIF-1 alpha was associated with the acquisition of resistance to gefitinib in NSCLC cell lines. Inhibition of HIF-1 alpha alleviated gefitinib resistance, indicating a potential strategy for developing anticancer drugs in combination with EGFR-TKIs for NSCLC patients.
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been used to treat patients with non-small cell lung cancer (NSCLC) and activating EGFR mutations; however, the emergence of secondary mutations in EGFR or the acquisition of resistance to EGFR-TKIs can develop and is involved in clinical failure. Since angiogenesis is associated with tumor progression and the blockade of antitumor drugs, inhibition of angiogenesis could be a rational strategy for developing anticancer drugs combined with EGFR-TKIs to treat patients with NSCLC. The signaling pathway mediated by hypoxia-inducible factor-1 (HIF-1) is essential for tumor angiogenesis. The present study aimed to identify the dependence of gefitinib resistance on HIF-1 alpha activity using angiogenesis assays, western blot analysis, colony formation assay, xenograft tumor mouse model and immunohistochemical analysis of tumor tissues. In the NSCLC cell lines, HIF-1 alpha protein expression levels and hypoxia-induced angiogenic activities were found to be increased. In a xenograft mouse tumor model, tumor tissues derived from gefitinib-resistant PC9 cells showed increased protein expression of HIF-1 alpha and angiogenesis within the tumors. Furthermore, inhibition of HIF-1 alpha suppressed resistance to gefitinib, whereas overexpression of HIF-1 alpha increased resistance to gefitinib. The results from the present study provides evidence that HIF-1 alpha was associated with the acquisition of resistance to gefitinib and suggested that inhibiting HIF-1 alpha alleviated gefitinib resistance in NSCLC cell lines.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据