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

Issue:

2023 21

Page:

3901-3907

Research Field:

Publishing date:

Info

Title:

PAK3 mediates Gefitinib resistance to non-small cell lung cancer by activating ERK1 activity

Author(s):

JIAO Haijing¹; LI Zhen²; 3; HUANG Shaobing²; 3; HAN Qiang²; 3; RONG Xuezhu²; 3; LIU Yang²; 3

1.Department of Clinical Laboratory,the Fourth Affiliated Hospital of China Medical University,Liaoning Shenyang 110001,China;2.Department of Pathology,Basic Medical Collegel of China Medical University,Liaoning Shenyang 110001,China;3.Department of Pathology,the First Hospital of China Medical University,Liaoning Shenyang 110001,China.

Keywords:

non-small cell lung cancer; Gefitinib resistance; PAK3; ERK1

PACS:

R734.2

DOI:

10.3969/j.issn.1672-4992.2023.21.001

Abstract:

Objective:To investigate the role and molecular mechanism of p21 activated kinase 3£¨PAK3£© in the Gefitinib resistance in non-small cell lung cancer(NSCLC).Methods:Using immunohistochemical methods,we compared the expression patterns of PAK3 in lung adenocarcinoma patients before and after Gefitinib resistance.Using Western Blot,we compared PAK3 expressionin lung cancer cell lines HCC827 and PC9 before and after Gefitinib resistance.After downregulating PAK3 in lung cancer cells using PAK3-siRNA,we detected the proliferation,invasion,and ERK1 activity by Western Blot and cellular functional experiments.After inhibiting the activity of ERK1,the PAK3-cDNA plasmid was transfected to detect the proliferation,invasion,and the sensitivity to Gefitinib.Results:PAK3 expression showed significantly increased in the lung cancer tissues and cell lines after Gefitinib resistance.PAK3 promoted the cell proliferation,invasion,and the related proteins expression in lung cancer cells.PAK3 activated the activity of ERK1 and reduced the sensitivity of lung cancer cell lines to Gefitinib.After inhibiting the activity of ERK1,upregulated PAK3 expression didn' t significantly promote the cell malignant phenotype and its Gefitinib resistance.Conclusion:PAK3 promotes the proliferation and invasion ability of lung cancer cells by activating ERK1,then promotes NSCLC resistance to Gefitinib.

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Memo

Memo:

National Natural Science Foundation of China(No.82003119£©£»¹ú¼Ò×ÔÈ»¿Æѧ»ù½ðÏîÄ¿(±àºÅ£º82003119)

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Last Update: 2023-09-28