中华微生物学和免疫学杂志
中華微生物學和免疫學雜誌
중화미생물학화면역학잡지
CHINESE JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY
2008年
4期
303-307
,共5页
郑天郢%王永刚%张昕%高雪芹%张华宁
鄭天郢%王永剛%張昕%高雪芹%張華寧
정천영%왕영강%장흔%고설근%장화저
白细胞介素8%表皮生长因子受体(EGFR)%G蛋白耦联受体(GPCR)%转激活%乳腺癌
白細胞介素8%錶皮生長因子受體(EGFR)%G蛋白耦聯受體(GPCR)%轉激活%乳腺癌
백세포개소8%표피생장인자수체(EGFR)%G단백우련수체(GPCR)%전격활%유선암
Interleukin-8%Epidermal growth factor receptor(EGFR)%G protein-coupled receptor(GPCR):Transactivation%Breast carcinoma
目的 探讨IL-8对乳腺癌细胞增殖和侵袭的影响以及IL-8信号通路与表皮生长因子受体(EGFR)信号通路之间的关系.方法 采用ELISA方法检测乳腺癌MDA-231细胞IL-8的分泌及rhEGF、anti-EGFR对IL-8分泌的影响;免疫细胞化学方法检测其膜受体CXCR1和CXCR2的表达;MTT和matrigel invasion(基质凝胶侵袭)方法分析rhIL-8及anti-IL-8对癌细胞增殖和侵袭的影响;Western blot分析rhlL-8及anti-IL-8对EGFR活化的影响.结果 乳腺癌细胞可分泌大量IL-8,其细胞膜表面表达CXCR1和CXCR2两种受体.rhlL-8及其中和抗体对乳腺癌细胞的增殖无明显影响,但可影响其侵袭能力:rhIL-8可提高癌细胞的侵袭活性(P<0.05),其中和抗体则对癌细胞的侵袭有抑制作用(P<0.05).rhEGF及anti-EGFR均明显抑制了MDA-231细胞IL-8的分泌(P<0.05,P<0.01);未发现rhIL-8对EGFR的酪氨酸磷酸化有任何影响,相反anti-IL-8却诱导了EGFR活化.结论 IL-8不是乳腺癌自分泌的促细胞生长因子,IL-8主要通过促进癌细胞的侵袭而影响肿瘤的发展.乳腺癌中G蛋白耦联受体(GPCR)介导的IL-8信号通路与EGFR信号通路之间并无cross-talk,而是竞争抑制的关系.
目的 探討IL-8對乳腺癌細胞增殖和侵襲的影響以及IL-8信號通路與錶皮生長因子受體(EGFR)信號通路之間的關繫.方法 採用ELISA方法檢測乳腺癌MDA-231細胞IL-8的分泌及rhEGF、anti-EGFR對IL-8分泌的影響;免疫細胞化學方法檢測其膜受體CXCR1和CXCR2的錶達;MTT和matrigel invasion(基質凝膠侵襲)方法分析rhIL-8及anti-IL-8對癌細胞增殖和侵襲的影響;Western blot分析rhlL-8及anti-IL-8對EGFR活化的影響.結果 乳腺癌細胞可分泌大量IL-8,其細胞膜錶麵錶達CXCR1和CXCR2兩種受體.rhlL-8及其中和抗體對乳腺癌細胞的增殖無明顯影響,但可影響其侵襲能力:rhIL-8可提高癌細胞的侵襲活性(P<0.05),其中和抗體則對癌細胞的侵襲有抑製作用(P<0.05).rhEGF及anti-EGFR均明顯抑製瞭MDA-231細胞IL-8的分泌(P<0.05,P<0.01);未髮現rhIL-8對EGFR的酪氨痠燐痠化有任何影響,相反anti-IL-8卻誘導瞭EGFR活化.結論 IL-8不是乳腺癌自分泌的促細胞生長因子,IL-8主要通過促進癌細胞的侵襲而影響腫瘤的髮展.乳腺癌中G蛋白耦聯受體(GPCR)介導的IL-8信號通路與EGFR信號通路之間併無cross-talk,而是競爭抑製的關繫.
목적 탐토IL-8대유선암세포증식화침습적영향이급IL-8신호통로여표피생장인자수체(EGFR)신호통로지간적관계.방법 채용ELISA방법검측유선암MDA-231세포IL-8적분비급rhEGF、anti-EGFR대IL-8분비적영향;면역세포화학방법검측기막수체CXCR1화CXCR2적표체;MTT화matrigel invasion(기질응효침습)방법분석rhIL-8급anti-IL-8대암세포증식화침습적영향;Western blot분석rhlL-8급anti-IL-8대EGFR활화적영향.결과 유선암세포가분비대량IL-8,기세포막표면표체CXCR1화CXCR2량충수체.rhlL-8급기중화항체대유선암세포적증식무명현영향,단가영향기침습능력:rhIL-8가제고암세포적침습활성(P<0.05),기중화항체칙대암세포적침습유억제작용(P<0.05).rhEGF급anti-EGFR균명현억제료MDA-231세포IL-8적분비(P<0.05,P<0.01);미발현rhIL-8대EGFR적락안산린산화유임하영향,상반anti-IL-8각유도료EGFR활화.결론 IL-8불시유선암자분비적촉세포생장인자,IL-8주요통과촉진암세포적침습이영향종류적발전.유선암중G단백우련수체(GPCR)개도적IL-8신호통로여EGFR신호통로지간병무cross-talk,이시경쟁억제적관계.
Objective To study the effect of IL-8 on cell proliferation and invasion,and to analyze the correlations between chemokine and epidermal growth factor receptor(EGFR)signaling pathways in breast carcinoma cells.Methods IL-8 secretion responded to treatment with rhEGF and anti-EGFR and expression of its receptors CXCR1,CXCR2 in MDA-231 cells were measured by ELISA and immunocytochemistry,respectively.Effect of rhIL-8 and neutralizing antibody on cell proliferation and invasion were analyzed by using MTT and matrigel invasion assay.EGFR transactivation stimulated with rhIL-8 and neutralizing an tibody was assessed by Western blot using anti-phosphotyrosine antibody.Results MDA-231 cells released hish level of IL-8 and two receptom of IL-8(CXCR1 and CXCR2)both expressed on cell membrane.Exogenous IL-8 and its neutralizing antibody did not significantly influence the proliferation of breast carcinoma cells,but rhIL-8 stimulated invasive activity in MDA-231 cells and its neutralizing antibody inhibited the in
vasive activity(P<0.05).EGF and anti-EGFR both inhibited the secretion of IL-8 in breast carcinoma cells,and IL-8 had no effect on EGFR phosphorylation,but anti-IL-8 induced transactivation of EGFR after 24h.Conclusion IL-8 contributes to tumor progression in breast carcinoma through its enhancement of in vasive activitv but not act as an autocrine growth factor.The correlation of competitive inhibition rather than cross-talk is found between G protein coupled receptor(GPCR)-mediated IL-8 signaling pathway and EGFR pathway in breast carcinoma.