Hyperoside exhibits anticancer activity in non-small cell lung cancer cells with T790M mutations by upregulating FoxO1 via CCAT1

被引:34
作者
Hu, Zhiyuan [1 ]
Zhao, Pengjun [2 ]
Xu, Huifang [3 ]
机构
[1] Zhuji Peoples Hosp, Dept Cardiothorac Surg, Zhuji 311800, Zhejiang, Peoples R China
[2] Hangzhou Canc Hosp, Dept Radiotherapy, Hangzhou 310002, Zhejiang, Peoples R China
[3] Zhejiang Hosp, Dept Oncol, 12 Lingyin Rd, Hangzhou 310013, Zhejiang, Peoples R China
关键词
hyperoside; lung cancer; long non-coding RNA; colon cancer associated transcript 1; FoxO1; PARIS SAPONIN I; APOPTOSIS; GEFITINIB; RESISTANCE; CISPLATIN; CASPASE-3; PATHWAY; GROWTH; LINE; PROLIFERATION;
D O I
10.3892/or.2019.7440
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Acquired epidermal growth factor receptor (EGFR) T790M mutation is the most common mechanism that accounts for EGFR-TKI (tyrosine kinase inhibitor) resistance of non-small cell lung cancer (NSCLC). High expense and acquired resistance weaken support for the use of osimertinib for T790M-positive NSCLC treatment, and limit the efficacy and application of this drug. Hyperoside, a flavonol glycoside compound, extracted from Hypericum perforatum, has been reported to inhibit the growth of a variety of tumors. The present study aimed to investigate the role of hyperoside in treating NSCLC with T790M mutations, and to elucidate the underlying molecular mechanisms. Cell viability assays, apoptosis analysis, reverse transcription-quantitative PCR, western blot analysis, animal experiments and immunohistochemistry were performed to examine the anticancer activity of hyperoside. Hyperoside inhibited the proliferation and induced the apoptosis of T790M-positive NSCLC cells. Hyperoside upregulated forkhead box protein O1 (FoxO1) expression and downregulated the level of long non-coding RNA (lncRNA) colon cancer associated transcript 1 (CCAT1) in T790M-positive NSCLC cells. In the in vivo study, hyperoside inhibited the growth of T790M-positive NSCLC xenografts. In conclusion, hyperoside inhibited proliferation and induced apoptosis by upregulating FoxO1 via CCAT1 in T790M-positive NSCLC both in vitro and in vivo, suggesting that hyperoside is a novel candidate for T790M-positive NSCLC treatment.
引用
收藏
页码:617 / 624
页数:8
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