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《Chinese Journal of Cancer Biotherapy》 2010-03
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Autocrined VEGF regulates mCRPs expressions in lung cancer cells and the related mechanisms

ZHAO Yong,ZHANG Ling,LI Cui-ling,YIN Hai-peng,GU Hong-tao,WEN Pei-e(Institute of Basic Medicine,Key Medical Laboratory for Tumor Immunology and Chinese Medicine Immunology of Shandong Province,Key Laboratory for Modern Medicine and Technology of Shandong Province,Shandong Academy of Medical Science,Ji′nan 250062,Shandong,China)  
Objective:To explore the regulatory effect of autocrined VEGF on membrane-bound complement regulatory proteins(mCRPs) expression in lung cancer A549 cells and the involved mechanisms.Methods: mRNA expressions of CD46,CD55,CD59,VEGF and their receptors(KDR and FLT-1),and IL-8 and its receptors(CXCR1 CXCR2) in A549 cells were detected by RT-PCR.The effects of anti-VEGF antibody and anti-IL-8 antibody on the proliferation and mCRPs expression in A549 cells were examined by MTT assay and flow cytometry,respectively.The effects of anti-VEGF antibody on the expression of transcription factor KLF2 and phospho-NF-κB p65 were examined by Western blotting analysis.Results: In addition to membrane CD46,CD55 and CD59 mRNA,both VEGF,IL-8 and their receptors(KDR,FLT-1;CXCR1,CXCR2) mRNA were expressed in A549 cells.Anti-VEGF antibody significantly inhibited the proliferation of A549 cells(P0.05).CD55 and CD59 mRNA and protein levels in A549 cells were decreased after treatment with 0.1 μg/ml anti-VEGF antibody for 72 h(P0.05).The relative values of KLF2 in cytoplasm and nuclear decreased from 0.63 and 0.88 to 0.42 and 0.66 after treatment with anti-VEGF antibody,while those of phospho-NF-κB p65 decreased from 0.44 and 0.28 to 0.32 and 0.19.Conclusion: VEGF may enhance CD55 and CD59 expressions in A549 cells through up-regulating expressions of NF-κB P65 and KLF2 transcription factors in an autocrine manner.
【Fund】: 山东省自然科学基金资助项目(No.Y2007C154)~~
【CateGory Index】: R734.2
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