非小细胞肺癌HCC827奥希替尼耐药细胞株的建立及耐药机制探讨

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Abstract Objective To construct human non-small cell lung cancer (NSCLC) Osimertinib-resistant cells HCC827OR in vitro, and to explore its resistance mechanism. Methods Using the NSCLC cell line HCC827, the Osimertinib-resistant cell line HCC827OR was constructed by the concentration-increasing method, and the differences in morphology, proliferation, apoptosis, and cell protein expression between the two cell lines were compared. Results Half-inhibitory concentration (IC50) and resistance index (RI) results showed that HCC827OR was highly resistant to Osimertinib, and the morphology of HCC827OR and HCC827 cells were significantly different. On the first day of the CCK8 proliferation experiment, the cell viability of HCC827OR was higher than that of HCC827 (P ＜ 0.05), and on the second, third and fourth days, the cell viability of HCC827OR was significantly higher than that of HCC827 (P ＜ 0.01). In the clone formation experiment result showed that, the colony formation number of HCC827OR was higher than that of HCC827 (P ＜ 0.01). After EdU staining, the number of EdU-positive cells in HCC827OR was higher than that in HCC827 (P ＜ 0.01). In the apoptosis experiment result showed that, compared with HCC827, the apoptosis of HCC827OR cells was reduced (P ＜ 0.01). In Western blot experiment, compared with HCC827, the expression of EGFR and p-EGFR in HCC827OR cells decreased, and the expression of p-AKT, p-ERK and Vimentin increased. Conclusion The NSCLC osimertinib-resistant cell line HCC827OR is successfully constructed. It is speculated that the resistance mechanism is related to the decreased expression of EGFR and p-EGFR, and the increased expression of p-AKT, p-ERK and Vimentin.

Key words： Non-small cell lung cancer Epidermal growth factor receptor tyrosine kinase inhibitor Osimertinib Drug resistance

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	HUANG Jiali CHEN Zhenyao LEI Tianyao WANG Zhaoxia CHENG Zhixiang

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HUANG Jiali CHEN Zhenyao LEI Tianyao WANG Zhaoxia CHENG Zhixiang. Establishment of non-small cell lung cancer HCC827 Osimertinib-resistant cell line and exploration of the resistance mechanism[J]. 中国医药导报, 2021, 18(14): 18-21,31.

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https://www.yiyaodaobao.com.cn/EN/ OR https://www.yiyaodaobao.com.cn/EN/Y2021/V18/I14/18

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