| Autor: |
Zhang Qianwen, Huang Huijing, Zheng Shuwen, Tang Yelin, Zhang Xiaodan, Zhu Qianqian, Ni Zefeng, Zheng Xiaohui, Wang Kun, Huang Lehao, Zhao Yunjie, Liu Zhiguo, Qian Jianchang |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Acta Biochimica et Biophysica Sinica, Vol 54, Pp 1540-1551 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1672-9145 |
| DOI: |
10.3724/abbs.2022139 |
| Popis: |
In recent decades, EGFR-targeted tyrosine kinase inhibitors (TKIs) have been proven to be an effective therapy for EGFR-mutant non-small cell lung cancer (NSCLC). However, resistance to EGFR-TKIs limits their clinical application. In the present study, we investigate the antitumor effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, cyy-287, in NSCLC. We find that cyy-287 has a high affinity for lung tissue and inhibits the proliferation of NSCLC cells. Interestingly, the significant suppression of migration and induction of apoptosis by cyy-287 are only observed in EGFR-driven but not in EGFR-wild-type (wt) cells. According to the RNA sequencing and KEGG enrichment analysis results, cyy-287 markedly inhibits the MAPK pathway in EGFR-driven PC9 cells, and western blot analysis results further indicate that cyy-287 selectively blocks the ERK pathway in EGFR-driven cells. Meanwhile, apoptosis induced by cyy-287 could be partially reversed by ERK pathway inhibition. Further experiment indicates that cyy-287 inhibits the EGFR pathway in both EGFR-driven and EGFR-overexpressing cells. Interestingly, it only induces apoptosis in EGFR-driven cells, not in EGFR-overexpressing cells. The growth of EGFR-driven cells is suppressed by cyy-287 in vivo, with fewer side effects. Our results suggest that cyy-287 may be a potential therapeutic drug with promising antitumor effects against NSCLC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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