南通大学学报(医学版)
南通大學學報(醫學版)
남통대학학보(의학판)
JOURNAL OF NANTONG UNIVERSITY(MEDICAL SCIENCES)
2014年
2期
81-84,85
,共5页
孟优%俞士尤%周俊东%陶敏
孟優%俞士尤%週俊東%陶敏
맹우%유사우%주준동%도민
结肠癌%二十二碳六烯酸%环氧合酶2%血管内皮细胞生长因子A%基质金属蛋白酶
結腸癌%二十二碳六烯痠%環氧閤酶2%血管內皮細胞生長因子A%基質金屬蛋白酶
결장암%이십이탄륙희산%배양합매2%혈관내피세포생장인자A%기질금속단백매
colorectal tumor%docosahexaenoic acid%cyclooxygenase 2%vascular endothelial growth factor-A%matrix metal-loproteinase
目的:探讨二十二碳六烯酸(docosahexaenoic acid,DHA)在抑制结肠癌发生、发展中的分子机制,为DHA新型抗癌药物的应用提供理论基础。方法:首先,建立人结肠癌裸鼠动物模型,观察DHA对裸鼠结肠癌移植瘤生长的影响;其次,应用半定量逆转录酶聚合酶链反应方法,检测环氧合酶2(cyclooxygenase 2,COX2)、低氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)、血管内皮细胞生长因子A(vascular endothelial growth factor-A,VEGF-A)、软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、固醇携带蛋白2(sterol carrier protein 2,SCP2)、多配体蛋白聚糖3(syndecan 3,SDC3)等多个与肿瘤发生发展密切相关基因的表达情况;最后,通过细胞水平实验对动物体内基因表达实验结果进行验证。结果:与对照组相比,DHA组裸鼠结肠癌移植瘤瘤块体积明显降低,证明DHA可以抑制结肠癌的发生发展;不管是在体内动物水平还是在体外细胞水平,DHA均可导致COX2、HIF-1α、VEGF-A、COMP、MMP-1、MMP-9、SCP2、SDC3基因表达水平明显降低。结论:DHA的抗癌作用涉及多方面、多层次的分子生物学机制。
目的:探討二十二碳六烯痠(docosahexaenoic acid,DHA)在抑製結腸癌髮生、髮展中的分子機製,為DHA新型抗癌藥物的應用提供理論基礎。方法:首先,建立人結腸癌裸鼠動物模型,觀察DHA對裸鼠結腸癌移植瘤生長的影響;其次,應用半定量逆轉錄酶聚閤酶鏈反應方法,檢測環氧閤酶2(cyclooxygenase 2,COX2)、低氧誘導因子-1α(hypoxia-inducible factor-1α,HIF-1α)、血管內皮細胞生長因子A(vascular endothelial growth factor-A,VEGF-A)、軟骨寡聚基質蛋白(cartilage oligomeric matrix protein,COMP)、基質金屬蛋白酶-1(matrix metalloproteinase-1,MMP-1)、基質金屬蛋白酶-9(matrix metalloproteinase-9,MMP-9)、固醇攜帶蛋白2(sterol carrier protein 2,SCP2)、多配體蛋白聚糖3(syndecan 3,SDC3)等多箇與腫瘤髮生髮展密切相關基因的錶達情況;最後,通過細胞水平實驗對動物體內基因錶達實驗結果進行驗證。結果:與對照組相比,DHA組裸鼠結腸癌移植瘤瘤塊體積明顯降低,證明DHA可以抑製結腸癌的髮生髮展;不管是在體內動物水平還是在體外細胞水平,DHA均可導緻COX2、HIF-1α、VEGF-A、COMP、MMP-1、MMP-9、SCP2、SDC3基因錶達水平明顯降低。結論:DHA的抗癌作用涉及多方麵、多層次的分子生物學機製。
목적:탐토이십이탄륙희산(docosahexaenoic acid,DHA)재억제결장암발생、발전중적분자궤제,위DHA신형항암약물적응용제공이론기출。방법:수선,건립인결장암라서동물모형,관찰DHA대라서결장암이식류생장적영향;기차,응용반정량역전록매취합매련반응방법,검측배양합매2(cyclooxygenase 2,COX2)、저양유도인자-1α(hypoxia-inducible factor-1α,HIF-1α)、혈관내피세포생장인자A(vascular endothelial growth factor-A,VEGF-A)、연골과취기질단백(cartilage oligomeric matrix protein,COMP)、기질금속단백매-1(matrix metalloproteinase-1,MMP-1)、기질금속단백매-9(matrix metalloproteinase-9,MMP-9)、고순휴대단백2(sterol carrier protein 2,SCP2)、다배체단백취당3(syndecan 3,SDC3)등다개여종류발생발전밀절상관기인적표체정황;최후,통과세포수평실험대동물체내기인표체실험결과진행험증。결과:여대조조상비,DHA조라서결장암이식류류괴체적명현강저,증명DHA가이억제결장암적발생발전;불관시재체내동물수평환시재체외세포수평,DHA균가도치COX2、HIF-1α、VEGF-A、COMP、MMP-1、MMP-9、SCP2、SDC3기인표체수평명현강저。결론:DHA적항암작용섭급다방면、다층차적분자생물학궤제。
Objective: To explore the underlying molecular mechanism of docosahexaenoic acid(DHA) inhibiting colorectal tumor pathogenesis, then to provide theoretical basis for application of DHA as a new anticarcinogen. Methods: A nude mice model with human colon cancer was conducted and effects of DHA feeding on growth of colorectal transplanted tumors in nude mice was observed. The expression of several genes correlated with tumorigenesis, including cyclooxygenase 2(COX2), hypoxia-inducible factor-1α(HIF-1α), vascular endothelial growth factor-A(VEGF-A), cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-1(MMP-1), matrix metalloproteinase-9(MMP-9), sterol carrier protein 2(SCP2), and syndecan 3(SDC3) were detected by semi-quantitative reverse transcriptase polymerase chain reaction in colorectal transplanted tumors of nude mice feeding with and without DHA. The influence of DHA on gene expression profiles in vivo was validated by in vitro experiment in HCT-16 cell line. Results: A significant decreased tumor size was observed in nude mice fed DHA. Both in vivo and in vitro results indicated that the expressions of these 8 target genes were significantly decreased by DHA treat-ment. Conclusion:It suggests that comprehensive and complicated mechanisms were involved in the antitumor functions of DHA.