JBRHA Special Issue n. 2, 2021, MS J119 (AHEAD OF PRINT)



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NT5E confers osimertinib resistance in non-small cell lung cancer by regulating epidermal growth factor receptor expression

QM. Li1#, QN. Zhao2#, Q. Liu3, HX. Li4, QJ. Wang5 and XL. Chen6

Author information

1Department of Respiratory, Zhangqiu District People’s Hospital, Jinan, China;
2Department of Clinical Laboratory, Yantaishan Hospital, Yantai, China;
3Department of Chinese Medicine, Zhangqiu District People’s Hospital, Jinan, China;
4Department of Anaesthesiology, Zhangqiu District People’s Hospital, Jinan, China;
5Department of Ophthalmology and Otorhinolaryngology, Zhangqiu Distrct People’s Hospital, Jinan, China;
6Department of Oncology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Lixia District, Jinan, Shandong, China

Abstract

NT5E is abnormally expressed in various tumors and is involved in the regulation of the occurrence and development of lung cancer (LC). The purpose of this study was to investigate the effect of overexpressing ecto-5′-nucleotidase (NT5E) on osimertinib (OSI) resistance in non-small cell lung cancer (NSCLC) PC-9 cells and its mechanism. Cell counting kit-8 (CCK-8) and colony formation assay were used to detect the sensitivity of NT5E to OSI in PC-9 cells. NT5E and epidermal growth factor receptor (EGFR) expression were detected by qRT-PCR and Western blotting. Immunohistochemistry (IHC) was used to detect the correlation between NT5E and EGFR expression in NSCLC tissues. The xenograft mouse model was established by injecting LV-NC and NT5E high-expressed PC-9 cells, and OSI intervention was given to investigate whether the high expression of NT5E would affect the inhibitory effect of OSI on tumor growth. After OSI treatment, the cell viability and colony formation of overexpressed NT5E group was significantly higher than that of the control group. It was found that NT5E overexpression could promote the expression of EGFR, and the OSI resistance induced by NT5E overexpression was reversed after the expression of EGFR was inhibited. IHC showed that NT5E and EGFR were correlated in NSCLC tissues. In vivo assays showed that NT5E overexpression facilitated tumor growth and enhanced the resistance of tumors to OSI in nude mice. Overexpression of NT5E enhanced OSI resistance of PC-9 cells, further confirming that NT5E was involved in drug resistance of NSCLC. NT5E was involved in OSI resistance in NSCLC by regulating EGFR expression.

Key words:

non-small cell lung cancer, NT5E, EGFR, osimertinib, PC-9

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