Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation
The epidermal growth factor receptor (EGFR) represents an effective target for the treatment of non-small cell lung cancer. In the treatment of classical EGFR mutations, EGFR tyrosine kinase inhibitors have achieved desirable clinical efficacy. However, the effectiveness of tyrosine kinase inhibitor...
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Elsevier
2024-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X24000471 |
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| author | Chunhong Chu Huixia Xu Chenxue Liu Xiangkai Wei Lanxin Li Rui Wang Wenrui Cui Guoliang Zhang Chenyang Liu Ke Wang Lei An Fei He |
| author_facet | Chunhong Chu Huixia Xu Chenxue Liu Xiangkai Wei Lanxin Li Rui Wang Wenrui Cui Guoliang Zhang Chenyang Liu Ke Wang Lei An Fei He |
| author_sort | Chunhong Chu |
| collection | DOAJ |
| description | The epidermal growth factor receptor (EGFR) represents an effective target for the treatment of non-small cell lung cancer. In the treatment of classical EGFR mutations, EGFR tyrosine kinase inhibitors have achieved desirable clinical efficacy. However, the effectiveness of tyrosine kinase inhibitors (TKIs) against the L861Q mutation has not been fully established. In this study, the four cell lines containing the L861Q mutation were constructed by CRISPR and the anti-tumour effects of CUDC-101 on them were investigated in vitro by various chemosensitivity methods, with afatinib serving as a positive control. The results demonstrated that CUDC-101 inhibited the proliferation and clonogenic capacity on the four cells through the ERK or AKT pathways, decreased the mitochondrial membrane potential of the cells, blocked the cell cycle and promoted apoptosis. Our findings suggest that CUDC-101 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation L861Q. |
| format | Article |
| id | doaj-art-a9f0224ccc3847c8b07b987fb4293eaf |
| institution | OA Journals |
| issn | 2666-027X |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj-art-a9f0224ccc3847c8b07b987fb4293eaf2025-08-20T02:37:48ZengElsevierCurrent Research in Toxicology2666-027X2024-01-01710019410.1016/j.crtox.2024.100194Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutationChunhong Chu0Huixia Xu1Chenxue Liu2Xiangkai Wei3Lanxin Li4Rui Wang5Wenrui Cui6Guoliang Zhang7Chenyang Liu8Ke Wang9Lei An10Fei He11Translational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, China; Institutes of Traditional Chinese Medicine, School of Pharmacy, Henan University, Kaifeng 475000, Henan, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, China; Institutes of Traditional Chinese Medicine, School of Pharmacy, Henan University, Kaifeng 475000, Henan, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, ChinaTranslational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, China; Institutes of Traditional Chinese Medicine, School of Pharmacy, Henan University, Kaifeng 475000, Henan, China; Corresponding authors at: No.115, Ximen Avenue, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, China.Translational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, China; Corresponding authors at: No.115, Ximen Avenue, Huaihe Hospital of Henan University, Henan University, Kaifeng 475000, China.The epidermal growth factor receptor (EGFR) represents an effective target for the treatment of non-small cell lung cancer. In the treatment of classical EGFR mutations, EGFR tyrosine kinase inhibitors have achieved desirable clinical efficacy. However, the effectiveness of tyrosine kinase inhibitors (TKIs) against the L861Q mutation has not been fully established. In this study, the four cell lines containing the L861Q mutation were constructed by CRISPR and the anti-tumour effects of CUDC-101 on them were investigated in vitro by various chemosensitivity methods, with afatinib serving as a positive control. The results demonstrated that CUDC-101 inhibited the proliferation and clonogenic capacity on the four cells through the ERK or AKT pathways, decreased the mitochondrial membrane potential of the cells, blocked the cell cycle and promoted apoptosis. Our findings suggest that CUDC-101 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation L861Q.http://www.sciencedirect.com/science/article/pii/S2666027X24000471L861QCUDC-101MutationProliferationCytotoxicology |
| spellingShingle | Chunhong Chu Huixia Xu Chenxue Liu Xiangkai Wei Lanxin Li Rui Wang Wenrui Cui Guoliang Zhang Chenyang Liu Ke Wang Lei An Fei He Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation Current Research in Toxicology L861Q CUDC-101 Mutation Proliferation Cytotoxicology |
| title | Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation |
| title_full | Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation |
| title_fullStr | Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation |
| title_full_unstemmed | Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation |
| title_short | Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation |
| title_sort | cytotoxicity and inhibitory potential of cudc 101 in non small cell lung cancer cells with rare egfr l861q mutation |
| topic | L861Q CUDC-101 Mutation Proliferation Cytotoxicology |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X24000471 |
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