|Table of Contents|

The role and mechanism of ABCG2 in osimertinib-resistant non-small cell lung cancer

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 06
Page:
1027-1034
Research Field:
Publishing date:

Info

Title:
The role and mechanism of ABCG2 in osimertinib-resistant non-small cell lung cancer
Author(s):
WANG Mei1; JIANG Junyao2; DU Yuxuan2; LIU Shuaimei2; GE Xiaojun1
1.Department of Laboratory Medicine,the Second Affiliated Hospital of Zunyi Medical University,Guizhou Zunyi 563000,China;2.School of Laboratory Medicine,Zunyi Medical University,Guizhou Zunyi 563000,China.
Keywords:
non-small cell lung cancer; osimertinib; ABCG2; EGFR
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.06.008
Abstract:
Objective：To explore the role of ABCG2 in NSCLC（non-small cell lung cancer） cells of drug resistance and the methods to reverse drug resistance.Methods:We chosed A549,NCI-H1299,NCI-1975 cells and induced them resistant to osimertinib,transfected lentiviral into A549,NCI-H1299 to make them have the T790M gene mutation,and induced them resistant to osimertinib.The IC50 value of osimertinib was detected by CCK-8 method.Intracellular osimertinib concentration detected by high performance liquid chromatography.Western-blot detection of intracellular EGFR,p-EGFR,ABCG2,AKT,p-AKT,PI3K,GSK,p-ERK and ERK protein expression.Gene sequencing detected mutations in exons of 18,19,20 and 21.The expression of ABCG2 in lung cancer cells was regulated by plasmid transfection and the sensitivity of cells to osimertinib was detected.Results:It was verified that the resistance coefficient was greater than 10 by CCK-8 method,it was proved that the construction of resistant cells was successful.The expression of ABCG2(ATP binding cassette subfamily G member 2) in osimertinib-resistant cells was increased and intracellular osimertinib concentration was decreased.It was found that the sensitivity of lung cancer cells to osimertinib decreased significantly after upregulating ABCG2 expression in lung cancer cells.Instead,the sensitivity to osimertinib was recovered after down-regulating the expression of ABCG2 in drug-resistant cells.The inhibition of both MAPK pathway and PI3K/AKT pathway can significantly inhibit the expression of ABCG2.Conclusion:The increase of ABCG2 expression is one of the important reasons for the resistance of non-small cell lung cancer to osimertinib.ABCG2 expression is related to MAPK and PI3K/AKT signaling pathway.

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Memo

Memo:
贵州省遵义市科技计划项目［编号：遵市科合HZ字（2019）35号］
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