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《Academic Journal of Second Military Medical University》 2017-02
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Association of lovastatin overcoming gefitinib resistance with integrin β1 and Survivin

JI Ze;PAN Xing;NI Dian-tao;SHANG Yan;BAI Chong;Department of Respiratory Medicine,Suzhou Kowloon Hospital,Shanghai Jiaotong University School of Medicine;Department of Nursing,Suzhou Kowloon Hospital,Shanghai Jiaotong University School of Medicine;Department of Respiratory and Critical Care Medicine,Changhai Hospital,Second Military Medical University;  
Objective To investigate the association of lovastatin overcoming gefitinib resistance with the levels of integrinβ1and Survivin in human non-small cell lung cancer(NSCLC)cell line PC9 in vitro,and to explore the possible mechanism.Methods The NSCLC cell line PC9 with acquired gefitinib-resistance were divided into 4groups:control group(RPMI 1640),gefitinib group(1μmol/L gefitinib),lovastatin group(5μmol/L lovastatin),and gefitinib combined with lovastatin group(1μmol/L gefitinib+5μmol/L lovastatin).After treatment with different drugs in each group,the inhibition of cell proliferation was detected by cell counting kit-8(CCK-8)test,the levels of integrinβ1and Survivin mRNA were detected by PCR,and the expressions of integrinβ1and Survivin protein were detected by Western blotting analysis.Results Compared with the control group,lovastatin group and gefitinib group,lovastatin combined with gefitinib treatment had significantly inhibited proliferation of PC9 cells with acquired gefitinib-resistance(P0.01),and the expressions of integrinβ1,Survivin protein and mRNA in PC9 cells were significantly decreased in the three groups(P0.05,P0.01).Conclusion Mechanisms of lovastatin combined with gefitinib in overcoming gefitinib resistance may be through blocking integrinβ1-p-Akt-Survivin signaling pathway,indicating that the combinationtreatment might be an effective strategy for gefitinib resistance.
【Fund】: 国家自然科学基金(81570020);; 教育部留学回国人员科研启动基金;; 浦东新区科技发展基金(PKJ2016-Y49);; 苏州工业园区孵化项目;; 浙江省公益技术应用研究计划项目(2016C33216)~~
【CateGory Index】: R734.2
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【Citations】
Chinese Journal Full-text Database 3 Hits
1 TAN Bi-bo;LI Yong;FAN Li-qiao;ZHAO Qun;WANG Dong;LIU Yu;The Third Department of Surgery,the Fourth Affiliated Hospital of Hebei Medical University;;Effect of Vav3 gene inhibition on inhibitor of apoptosis proteins and multidrug resistance in gastric cancer cells[J];第二军医大学学报;2015-02
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【Co-citations】
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1 NAN Zhenhua;PAN Linghui;Department of Anesthesiology, Affiliated Cancer Hospital, Guangxi Medical University;;Mechanism of Ibuprofen Regulating Migration and Invasion of Liver Cancer QGY-7703 Cells Through PI3K/Akt/mTOR Signaling Pathway[J];肿瘤防治研究;2016-12
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