| Status | 已發表Published |
| Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells | |
Tang, ZH ; Su, MX; Cao, WX; Chen, X. P.; Lu, J. 
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| 2016-12-01 | |
| Source Publication | The 5th GuangZhou international symposium oncology, the 1st annual symposium of the Chinese Association of targeted therapy in oncology
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| Abstract | Objective: To investigate the effects and mechanisms of Osimertinib (OSI, also known as AZD9291)-induced autophagy and apoptosis in non-small cell lung cancer cells. Methods: The accumulations of cytoplasmic vacuoles were observed through inverted microscope. The expressions of proteins were detected through western blot. The formations of GFP-LC3 and mRFP-GFP-LC3 puncta were observed by using fluorescence microscope. ROS generation was detected by using fluorescent probe CM-DCFH2-DA. The apoptotic cells were detected by using annexin V-FITC/PI staining and western blot assays. The cell viability was detected through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Results: We indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells. OSI-induced expression of LC3-II was increased when combined with chloroquine (CQ), an autophagy inhibitor, and the mRFP-GFP-LC3 plasmid-transfected cells exposed to OSI led to the production of red-fluorescent puncta, indicating OSI induced autophagic flux in NSCLC cells. Knockdown of EGFR showed no effect on OSI-induced LC3-II expression in NCI-H1975 cells. In addition, OSI increased reactive oxygen species (ROS) generation and scavenge of ROS via pretreatment with N-acetyl-L-cysteine (NAC) significantly inhibited OSI-induced accumulations of cytoplasmic vacuoles, expression of LC3-II, as well as formation of GFP-LC3 puncta. Combinative treatment with CQ could not remarkably change OSI-induced cell viability decrease, whereas OSI-induced cell viability decrease and apoptosis could be reversed through pretreatment with NAC. Conclusion: This is the first report that OSI-induced an accompanied autophagy and the generation of ROS is critical for OSI-induced autophagy, cell viability decrease, and apoptosis in NSCLC cells. |
| Keyword | Osimertinib AZD9291 autophagy apoptosis NSCLC |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 36499 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Lu, J. |
| Recommended Citation GB/T 7714 | Tang, ZH,Su, MX,Cao, WX,et al. Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells[C], 2016. |
| APA | Tang, ZH., Su, MX., Cao, WX., Chen, X. P.., & Lu, J. (2016). Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells. The 5th GuangZhou international symposium oncology, the 1st annual symposium of the Chinese Association of targeted therapy in oncology. |
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