The Experimental Study Of PAK Group?Affects The Sensitivity Of Lung Cancer Cells To EGFR-TKI And The Role Of PAK1 In Proliferation And Invasion Of Lung Cancer Cells

Objective: EGFR-TKI,represented by gefitinib,is an effective treatment for NSCLC.But with the prolongation of the use of time,the sensitivity of gefitinib to patient is gradually decreased.PAK is an evolutionarily conserved serine/threonine protein kinase.Current studies have shown that the expression of PAK may affect the sensitivity of gefitinib to patients,and that changes in the expression of some of its members may lead to changes in the proliferation and invasiveness of cancer cells.This article aims to investigate the expression of PAK and its significance in NSCLC.Methods: In the first part of this study,PAK Group I and PAK Group II immunohistochemical staining were performed on 182 pathological specimens of NSCLC and normal lung tissues from the First Affiliated Hospital of China Medical University.Western blot was used to detect in HBE,A549,NCI-H1299,LK-2 and SK-MES-1 cell lines.After that,we treated lung cancer cells with PAK Group I inhibitor IPA3,and then treated them with gefitinib.The proliferation of lung cancer cells was detected by MTT assay twice.In the second part of this study,we detected the expression of PAK1 by immunohistochemistry and Western blot.After reducing the expression of PAK1 by si RNA,MTT assay was used to detect the change of proliferation ability and Transwell migration assay was used to detect the change of invasion ability.Results:Immunohistochemical and Western blot results showed that PAK Group I and PAK Group II were overexpressed in NSCLC.PAK Group I was overexpressed in cytoplasm,and PAK Group II was mainly expressed in nucleus.Inhibition of PAK Group I activity by IPA3 can reduce the proliferation of lung cancer cells.IPA3 plus gefitinib treated cells can inhibit the proliferation of lung cancer cells more than one single of them treated cells.Later studies on PAK1 showed that PAK1 was overexpressed in NSCLC,mainly expression in cytoplasm.Inhibition of PAK1 expression by si RNA decreased the proliferation and invasiveness of NSCLC cells.Conclusion:PAK Group I,PAK Group II and PAK1 were overexpressed in NSCLC.The inhibition of activity about PAK Group I promotes the sensitivity of NSCLC to EGFR-TKIs.Decreased PAK1 activity inhibits proliferation and invasion of NSCLC.