https://scholars.lib.ntu.edu.tw/handle/123456789/639941
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Wang, Su-Pei | en_US |
dc.contributor.author | Hsu, Ya-Ping | en_US |
dc.contributor.author | CHIEN-JEN CHANG | en_US |
dc.contributor.author | Chan, Yu-Chi | en_US |
dc.contributor.author | Chen, Chien-Hung | en_US |
dc.contributor.author | Wang, Rou-Hsin | en_US |
dc.contributor.author | Liu, Kuang-Kai | en_US |
dc.contributor.author | Pan, Pei-Ying | en_US |
dc.contributor.author | Wu, Ya-Hui | en_US |
dc.contributor.author | Yang, Chih-Man | en_US |
dc.contributor.author | Chen, Chinpiao | en_US |
dc.contributor.author | Yang, Jinn-Moon | en_US |
dc.contributor.author | Liang, Mei-Chih | en_US |
dc.contributor.author | Wong, Kwok-Kin | en_US |
dc.contributor.author | Chao, Jui-I | en_US |
dc.date.accessioned | 2024-02-26T07:16:08Z | - |
dc.date.available | 2024-02-26T07:16:08Z | - |
dc.date.issued | 2021-11 | - |
dc.identifier.issn | 00062952 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/639941 | - |
dc.description.abstract | Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are currently used therapy for non-small cell lung cancer (NSCLC) patients; however, drug resistance during cancer treatment is a critical problem. Survivin is an anti-apoptosis protein, which promotes cell proliferation and tumor growth that highly expressed in various human cancers. Here, we show a novel synthetic compound derived from gefitinib, do-decyl-4-(4-(3-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)propyl) piper-azin-1-yl)-4-oxobutanoate, which is named as SP101 that inhibits survivin expression and tumor growth in both the EGFR-wild type and -T790M of NSCLC. SP101 blocked EGFR kinase activity and induced apoptosis in the A549 (EGFR-wild type) and H1975 (EGFR-T790M) lung cancer cells. SP101 reduced survivin proteins and increased active caspase 3 for inducing apoptosis. Ectopic expression of survivin by a survivin-expressed vector attenuated the SP101-induced cell death in lung cancer cells. Moreover, SP101 inhibited the gefitinib-resistant tumor growth in the xenograft human H1975 lung tumors of nude mice. SP101 substantially reduced survivin proteins but conversely elicited active caspase 3 proteins in tumor tissues. Besides, SP101 exerted anticancer abilities in the gefitinib resistant cancer cells separated from pleural effusion of a clinical lung cancer patient. Consistently, SP101 decreased the survivin proteins and the patient-derived xenografted lung tumor growth in nude mice. Anti-tumor ability of SP101 was also confirmed in the murine lung cancer model harboring EGFR T790M-L858R. Together, SP101 is a new EGFR inhibitor with inhibiting survivin that can be developed for treating EGFR wild-type and EGFR-mutational gefitinib-resistance in human lung cancers. | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Biochemical pharmacology | en_US |
dc.subject | Drug resistance; EGFR inhibitor; Non-small cell lung cancer; Survivin; Tumor growth | en_US |
dc.title | A novel EGFR inhibitor suppresses survivin expression and tumor growth in human gefitinib-resistant EGFR-wild type and -T790M non-small cell lung cancer | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1016/j.bcp.2021.114792 | - |
dc.identifier.pmid | 34597670 | - |
dc.identifier.scopus | 2-s2.0-85116939688 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/85116939688 | - |
dc.relation.journalvolume | 193 | en_US |
item.fulltext | no fulltext | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
item.openairetype | journal article | - |
item.languageiso639-1 | en | - |
crisitem.author.dept | Internal Medicine-NTUHHC | - |
crisitem.author.orcid | 0000-0001-7700-1325 | - |
crisitem.author.parentorg | NTU Hsin-Chu Hospital | - |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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