| Status | 已發表Published |
| Treatment of osimertinib (AZD9291)-resistant non-small cell lung cancer HCC827/OSIR cells by targeting inositol-requiring enzyme 1α | |
Tang, ZH ; Su, MX; Guo, XH; Jiang, XM; Chen, X. P.; Lu, J. 
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| 2016-11-01 | |
| Source Publication | The Fourth Symposium on New Trends in Individualized Therapy and Antineoplastic Agents
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| Abstract | Objective: The third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib (OSI, also known as AZD9291) has been approved for treatment of EGFR T790M positive mutation NSCLC patients who has progressed after gefitinib or erlotinib treatment. Whether or not OSI can be used as the first option for NSCLC patients with naive EGFR sensitive mutation was controversial. Methods: The OSI-resistant HCC827/OSIR cells were established on HCC827 cells (cells with naive EGFR sensitive mutation) by dose escalation method. The resistant effect of HCC827/OSIR cells were confirmed by MTT and colony formation assays. The protein expression was determined by western blot assay. The morphology was observed using a microscope. The trypan blue staining assay was used to count the viable cell numbers. Results: The HCC-827/OSIR cells were more resistant to other EGFR TKIs, such as, gefitinib, erlotinib, afatinib, as well as rociletinib, when compared with HCC827 cells. The anti-proliferation of pemetrexed, doxorubicin, and fluorouracil in HCC827 and HCC827/OSIR cells were similar, while the cytotoxicity of paclitaxel was more remarkable in HCC827/OSIR cells than that in HCC827 cells. In addition, the expression of inositol-requiring enzyme 1α (IRE1α) was increased after cells developed resistance to OSI. Knockdown of IRE1α by siRNA or pretreatment with STF-083010, an IRE1α inhibitor, decreased the viable cell numbers in both cell lines, especially in HCC827/OSIR cells. Conclusion: OSI may be not suitable as the first option for NSCLC patients who harboring naive EGFR sensitive mutation based on the results we observed and target of IRE1α might be one of potential therapy strategies for treatment of OSI-resistant NSCLC. |
| Keyword | osimertinib AZD9291 EGFR IRE1α NSCLC |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 36497 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Lu, J. |
| Recommended Citation GB/T 7714 | Tang, ZH,Su, MX,Guo, XH,et al. Treatment of osimertinib (AZD9291)-resistant non-small cell lung cancer HCC827/OSIR cells by targeting inositol-requiring enzyme 1α[C], 2016. |
| APA | Tang, ZH., Su, MX., Guo, XH., Jiang, XM., Chen, X. P.., & Lu, J. (2016). Treatment of osimertinib (AZD9291)-resistant non-small cell lung cancer HCC827/OSIR cells by targeting inositol-requiring enzyme 1α. The Fourth Symposium on New Trends in Individualized Therapy and Antineoplastic Agents. |
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