癌症
癌癥
암증
CHINESE JOURNAL OF CANCER
2010年
1期
32-37
,共6页
梅开%蔡晓虹%杜磊%陈艳芳%黄霜%陈晶%尹序德%张芷旋%赵新%周澄亚%喻璟瑞
梅開%蔡曉虹%杜磊%陳豔芳%黃霜%陳晶%尹序德%張芷鏇%趙新%週澄亞%喻璟瑞
매개%채효홍%두뢰%진염방%황상%진정%윤서덕%장지선%조신%주징아%유경서
一氧化氮合成酶%内皮型%血管内皮生长因子%内皮祖细胞%肿瘤血管
一氧化氮閤成酶%內皮型%血管內皮生長因子%內皮祖細胞%腫瘤血管
일양화담합성매%내피형%혈관내피생장인자%내피조세포%종류혈관
endothelial nitric oxide synthase%nitric oxide%endothelial progenitorcells%tumor angiogenesis%vascular endothelial growth factor
背景与目的:内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)来源的一氧化氮(nitric oxicle,NO)广泛表达于肿瘤组织,调节着肿瘤血管的生长,但研究结果并不一致.本研究中探讨NO对肿瘤血管形成的作用及其机制.方法:将C57BL/6小鼠随机分为3组:NO组小鼠右胁下接种eNOS基因转染的Lewis肺癌细胞;eNOS拮抗组小鼠接种Lewis肺癌细胞后腹腔注射eNOS拮抗剂L-NAME;对照组接种Lewis肺癌细胞后注射同等体积的生理盐水.处理3周后,测定血浆内NO含量,计数外周血中内皮祖细胞(EPC)数;取肿瘤组织测定每高倍视野下(HPF)血管密度、EPC细胞数量和血管内皮细胞生长因子及其受体复合物(VEGF-VEGFR)的表达.结果:接种Lewis细胞4周后,对照组肿瘤体积为(3022±401)mm~3,而L-NAME组和eNOS组分别为(1204±97)mm~3和(1824±239)mm~3,三组比较有显著性差异(P<0.01).eNOS基因转染组肿瘤组织内eNOS蛋白表达和NO的生成显著高于对照组,但肿瘤组织中EPC数量[(48±19)/HPF]、血管密度[(19±7)/HPF]显著低于对照组(P<0.05),循环EPC数量与对照组比较无显著变化.L-NAME腹腔注射能显著减少血液及肿瘤组织内NO浓度,循环EPC数量和肿瘤组织内EPC数量也随之显著降低,肿瘤血管密度也降至(12±5)/HPF,与对照组及eNOS转染组比较差异有统计学意义(P<0.05).结论:eNOS来源的NO低表达和高表达时都能通过减少VEGF与其受体的结合而抑制EPC参与的肿瘤新生血管的生成和肿瘤的生长.
揹景與目的:內皮型一氧化氮閤酶(endothelial nitric oxide synthase,eNOS)來源的一氧化氮(nitric oxicle,NO)廣汎錶達于腫瘤組織,調節著腫瘤血管的生長,但研究結果併不一緻.本研究中探討NO對腫瘤血管形成的作用及其機製.方法:將C57BL/6小鼠隨機分為3組:NO組小鼠右脅下接種eNOS基因轉染的Lewis肺癌細胞;eNOS拮抗組小鼠接種Lewis肺癌細胞後腹腔註射eNOS拮抗劑L-NAME;對照組接種Lewis肺癌細胞後註射同等體積的生理鹽水.處理3週後,測定血漿內NO含量,計數外週血中內皮祖細胞(EPC)數;取腫瘤組織測定每高倍視野下(HPF)血管密度、EPC細胞數量和血管內皮細胞生長因子及其受體複閤物(VEGF-VEGFR)的錶達.結果:接種Lewis細胞4週後,對照組腫瘤體積為(3022±401)mm~3,而L-NAME組和eNOS組分彆為(1204±97)mm~3和(1824±239)mm~3,三組比較有顯著性差異(P<0.01).eNOS基因轉染組腫瘤組織內eNOS蛋白錶達和NO的生成顯著高于對照組,但腫瘤組織中EPC數量[(48±19)/HPF]、血管密度[(19±7)/HPF]顯著低于對照組(P<0.05),循環EPC數量與對照組比較無顯著變化.L-NAME腹腔註射能顯著減少血液及腫瘤組織內NO濃度,循環EPC數量和腫瘤組織內EPC數量也隨之顯著降低,腫瘤血管密度也降至(12±5)/HPF,與對照組及eNOS轉染組比較差異有統計學意義(P<0.05).結論:eNOS來源的NO低錶達和高錶達時都能通過減少VEGF與其受體的結閤而抑製EPC參與的腫瘤新生血管的生成和腫瘤的生長.
배경여목적:내피형일양화담합매(endothelial nitric oxide synthase,eNOS)래원적일양화담(nitric oxicle,NO)엄범표체우종류조직,조절착종류혈관적생장,단연구결과병불일치.본연구중탐토NO대종류혈관형성적작용급기궤제.방법:장C57BL/6소서수궤분위3조:NO조소서우협하접충eNOS기인전염적Lewis폐암세포;eNOS길항조소서접충Lewis폐암세포후복강주사eNOS길항제L-NAME;대조조접충Lewis폐암세포후주사동등체적적생리염수.처리3주후,측정혈장내NO함량,계수외주혈중내피조세포(EPC)수;취종류조직측정매고배시야하(HPF)혈관밀도、EPC세포수량화혈관내피세포생장인자급기수체복합물(VEGF-VEGFR)적표체.결과:접충Lewis세포4주후,대조조종류체적위(3022±401)mm~3,이L-NAME조화eNOS조분별위(1204±97)mm~3화(1824±239)mm~3,삼조비교유현저성차이(P<0.01).eNOS기인전염조종류조직내eNOS단백표체화NO적생성현저고우대조조,단종류조직중EPC수량[(48±19)/HPF]、혈관밀도[(19±7)/HPF]현저저우대조조(P<0.05),순배EPC수량여대조조비교무현저변화.L-NAME복강주사능현저감소혈액급종류조직내NO농도,순배EPC수량화종류조직내EPC수량야수지현저강저,종류혈관밀도야강지(12±5)/HPF,여대조조급eNOS전염조비교차이유통계학의의(P<0.05).결론:eNOS래원적NO저표체화고표체시도능통과감소VEGF여기수체적결합이억제EPC삼여적종류신생혈관적생성화종류적생장.
Background and Objective:Studies have shown that nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is expressed widely in tumor tissues and regulates tumor angiogenesis.However,the results are controversial.This study was to investigate the effect of NO on tumor angiogenesis and its mechanism.Methods:C57BL/6 mice inoculated with Lewis lung cancer cells were randomly divided into three groups.Mice in the NO group were inoculated with lung cancer cells transfected with eNOS gene,mice in the L-NAME group with L-NAME,an eNOS antagonist,and mice in the control group with normal saline.Plasma concentration of NO and the number of endothelial progenitor cells (EPCs) in peripheral blood were detected.Tumor vessel density,CD133* cells,and the expression of VEGF-VEGFR in tumor tissues were also measured.Results.Four weeks after inoculation of Lewis cells,tumor volume was significantly larger in control group [(3022±401) mm~3] than in the L-NAME group [(1204±97) mm~3] and in the eNOS group [(1824±239) mm~3] (P<0.01).eNOS protein and NO production increased significantly in Lewis lung cancer cells transfected with eNOS gene.But the number of CD133-positive cells and vessel density in tumors were significantly lower in the eNOS group than in the control group [(48±19)/HPF vs.(103±27)/HPF,(19±7)/HPF vs.(31±9)/HPF,P<0.05].The number of EPCs in peripheral blood was not statistically different between each group.The levels of NO in blood and tumor tissue significantly decreased after the treatment of L-NAME,while the tumor vessel density reduced to 12±5/HPF (P<0.01,vs.the control group; P<0.05,vs.the eNOS transfected group).The number of EPCs in blood and that of CD133-positive cells in tumor tissue were significantly smaller in the L-NAME group than in the control group (P<0.05).Conclusion:NO derived from eNOS inhibits angiogenesis and tumor growth,which may be due to its suppression on either the mobilization or homing of EPCs via VEGF binding to VEGFR.
