CAJ | 학술논문

目的：探讨ω-3多不饱和脂肪酸对人胃腺癌 AGS 细胞生长增殖的作用和可能的机制。方法以不同浓度梯度的 DHA、EPA 作用于体外培养的 AGS 细胞和人微血管内皮细胞 HMEC-1,采用四甲基偶氮唑蓝(MTT)观察细胞增殖抑制率,使用流式细胞仪检测细胞周期变化,采用 Western blot 分析细胞线粒体呼吸链膜蛋白复合体Ⅰ、Ⅱ、Ⅴ表达变化。结果DHA 和 EPA 对胃腺癌 AGS 细胞增殖具有明显抑制作用,该抑制作用呈现明显的剂量时间依赖效应的特点(P <0.05),在相同的浓度梯度下,DHA 的抑制作用强于 EPA(P <0.05)。倒置显微镜下 DHA 作用后观察到AGS 细胞明显皱缩,细胞的贴壁能力明显减弱。流式细胞仪检测显示,DHA、EPA 干预后 AGS 细胞的 DNA 合成前期(G0/G1期)细胞分布比例明显增加,DNA 合成期(S 期)细胞分布比例明显减少(P <0.05)。Western blot 分析可见,DHA 干预 AGS 细胞24 h 和48 h 后,与对照组比较,AGS 线粒体呼吸链膜蛋白复合体Ⅰ、Ⅱ、Ⅴ表达灰度值显著下降,而且随着作用时间延长,复合体表达灰度值下降愈明显(P <0.05)。DHA 对人微血管内皮细胞的生长增殖、细胞形态和线粒体呼吸链膜蛋白复合体无明显影响(P >0.05)。结论ω-3多不饱和脂肪酸可选择性有效地抑制人胃腺癌 AGS 细胞的生长增殖。该作用可能是通过阻滞 AGS 细胞于 G0/G1期和抑制 AGS 细胞能量代谢来实现的。
목적：탐토ω-3다불포화지방산대인위선암 AGS 세포생장증식적작용화가능적궤제。방법이불동농도제도적 DHA、EPA 작용우체외배양적 AGS 세포화인미혈관내피세포 HMEC-1,채용사갑기우담서람(MTT)관찰세포증식억제솔,사용류식세포의검측세포주기변화,채용 Western blot 분석세포선립체호흡련막단백복합체Ⅰ、Ⅱ、Ⅴ표체변화。결과DHA 화 EPA 대위선암 AGS 세포증식구유명현억제작용,해억제작용정현명현적제량시간의뢰효응적특점(P <0.05),재상동적농도제도하,DHA 적억제작용강우 EPA(P <0.05)。도치현미경하 DHA 작용후관찰도AGS 세포명현추축,세포적첩벽능력명현감약。류식세포의검측현시,DHA、EPA 간예후 AGS 세포적 DNA 합성전기(G0/G1기)세포분포비례명현증가,DNA 합성기(S 기)세포분포비례명현감소(P <0.05)。Western blot 분석가견,DHA 간예 AGS 세포24 h 화48 h 후,여대조조비교,AGS 선립체호흡련막단백복합체Ⅰ、Ⅱ、Ⅴ표체회도치현저하강,이차수착작용시간연장,복합체표체회도치하강유명현(P <0.05)。DHA 대인미혈관내피세포적생장증식、세포형태화선립체호흡련막단백복합체무명현영향(P >0.05)。결론ω-3다불포화지방산가선택성유효지억제인위선암 AGS 세포적생장증식。해작용가능시통과조체 AGS 세포우 G0/G1기화억제 AGS 세포능량대사래실현적。
ABSTRACT:Objective To investigate the effects of ω-3 polyunsaturated fatty acids on the proliferation of human gastric cancer cell line AGS and the possible mechanisms.Methods Human gastric cancer line AGS and human microvascular epithelial cell HMEC-1 were treated with different concentrations of docosdhexaenoic acid (DHA)and eicosapentaenoic acid (EPA).The inhibition of cell proliferation was evaluated by MTT assay and cell morphology.Flow cytometry was used to detect the cell cycle change.The expressions of mitochondrial respiratory membrane protein complex Ⅰ,Ⅱ and V were analyzed with Western blot.Results DHA and EPA could markedly inhibit the proliferation of AGS in significant time-dependent and concentration-dependent manners (P < 0.05 ). The inhibitory effect of DHA was stronger than that of EPA under the same concentration gradient (P <0.05).The morphological changes of cells were characterized by cell shrinkage and weak adhesion.Flow cytometry showed that AGS cells treated with DHA and EPA were arrested in G0/G1 phase and the proportion of AGS cells in G0/G1 phase increased compared with that of the control group while the proportion of the cells in S phase decreased significantly (P <0.05).Western blot showed after treatment with DHA for 24 h and 48 h,compared with control group,the expressions of mitochondrial respiratory membrane protein complex Ⅰ,Ⅱ and Ⅴ were obviously decreased.The longer effect of DHA,the lower expression of membrane protein complex (P <0.05).DHA had little effect on cell proliferation,morphology or mitochondrial membrane protein complex in HMEC-1 (P >0.05).Conclusion ω-3 PUFAs can selectively inhibit the growth and proliferation of human gastric cancer cell line AGS.These effects may be as-sociated with arresting cell cycle in G0/G1 phase and inhibiting the energy metabolism of AGS cells.