中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2013年
10期
2046-2048
,共3页
韩菲菲%王婷婷%杨小娟%梁加贝%陈国千
韓菲菲%王婷婷%楊小娟%樑加貝%陳國韆
한비비%왕정정%양소연%량가패%진국천
高迁移率族蛋白B1%癌,肝细胞%缺氧%丝裂原活化蛋白激酶信号通路
高遷移率族蛋白B1%癌,肝細胞%缺氧%絲裂原活化蛋白激酶信號通路
고천이솔족단백B1%암,간세포%결양%사렬원활화단백격매신호통로
High mobility group protein B1 protein%Carcinoma,hepatocellular%Hypoxia%Mitogen-activated protein kinase signaling system
目的 探讨缺氧对肝癌细胞高迁移率族蛋白B1(HMGB1)释放的诱导作用及其机制.方法 采用正常肝细胞株QSG-7701和肝癌细胞株SMMC-7721,观察缺氧(1％O2)培养3～24h后对HMGB1胞外释放、HMGB1基因表达和HMGB1胞内分布的影响,使用丝裂原活化蛋白激酶(MAPK)通路抑制剂探讨缺氧诱导HMGB1释放的机制.观察28例肝细胞癌患者血清HMGB1水平的改变.结果 肝细胞癌患者血清HMGB1水平[(19.3±7.2) μg/L]明显高于健康对照者[(4.1±1.6) μg/L,P＜0.01].QSG-7701和SMMC-7721细胞经缺氧培养后,3h即见培养上清液中HMGB1含量明显升高,HMGB1 mRNA表达于6h后显示增强,且SMMC-7721株改变更为显著.SMMC-7721细胞经缺氧培养12 h后,核浆HMGB1分布发生明显改变,胞质HMGB1蛋白表达量升高.SB203580、SP600125和PD98059对缺氧诱导HMGB1释放均显示不同程度的抑制作用.结论 缺氧能诱导肝癌细胞表达、释放HMGB1,其诱导HMGB1释放机制与MAPK信号通路有关.
目的 探討缺氧對肝癌細胞高遷移率族蛋白B1(HMGB1)釋放的誘導作用及其機製.方法 採用正常肝細胞株QSG-7701和肝癌細胞株SMMC-7721,觀察缺氧(1％O2)培養3～24h後對HMGB1胞外釋放、HMGB1基因錶達和HMGB1胞內分佈的影響,使用絲裂原活化蛋白激酶(MAPK)通路抑製劑探討缺氧誘導HMGB1釋放的機製.觀察28例肝細胞癌患者血清HMGB1水平的改變.結果 肝細胞癌患者血清HMGB1水平[(19.3±7.2) μg/L]明顯高于健康對照者[(4.1±1.6) μg/L,P＜0.01].QSG-7701和SMMC-7721細胞經缺氧培養後,3h即見培養上清液中HMGB1含量明顯升高,HMGB1 mRNA錶達于6h後顯示增彊,且SMMC-7721株改變更為顯著.SMMC-7721細胞經缺氧培養12 h後,覈漿HMGB1分佈髮生明顯改變,胞質HMGB1蛋白錶達量升高.SB203580、SP600125和PD98059對缺氧誘導HMGB1釋放均顯示不同程度的抑製作用.結論 缺氧能誘導肝癌細胞錶達、釋放HMGB1,其誘導HMGB1釋放機製與MAPK信號通路有關.
목적 탐토결양대간암세포고천이솔족단백B1(HMGB1)석방적유도작용급기궤제.방법 채용정상간세포주QSG-7701화간암세포주SMMC-7721,관찰결양(1％O2)배양3～24h후대HMGB1포외석방、HMGB1기인표체화HMGB1포내분포적영향,사용사렬원활화단백격매(MAPK)통로억제제탐토결양유도HMGB1석방적궤제.관찰28례간세포암환자혈청HMGB1수평적개변.결과 간세포암환자혈청HMGB1수평[(19.3±7.2) μg/L]명현고우건강대조자[(4.1±1.6) μg/L,P＜0.01].QSG-7701화SMMC-7721세포경결양배양후,3h즉견배양상청액중HMGB1함량명현승고,HMGB1 mRNA표체우6h후현시증강,차SMMC-7721주개변경위현저.SMMC-7721세포경결양배양12 h후,핵장HMGB1분포발생명현개변,포질HMGB1단백표체량승고.SB203580、SP600125화PD98059대결양유도HMGB1석방균현시불동정도적억제작용.결론 결양능유도간암세포표체、석방HMGB1,기유도HMGB1석방궤제여MAPK신호통로유관.
Objective To investigate the effect of hypoxia on extracellular release of high mobility group box 1 (HMGB1) in hepatocellular carcinoma (HCC) cells and its mechanisms.Methods Using hepatocytes QSG-7701 and HCC cells SMMC-7721,the effect of hypoxia (1％ O2,3-24 h) on HMGB1 release,HMGB1 mRNA expression and the intracellular distribution of HMGB1 was observed.Mitogen-activated protein kinase (MAPK) pathway inhibitors were used to explore the mechanisms of hypoxia-induced HMGB1 release.Serum HMGB1 levels in 28 HCC patients were detected.Results Serum HMGB1 levels in HCC patients [(19.3 ±7.2) pμg/L] were significantly higher than those in healthy controls [(4.1 ± 1.6) μg/L,P ＜0.01].HMGB1 concentration in the culture supernatant was narkedly increased at 3 h,and HMGB1 mRNA expression began to increase at 6 h,after QSG-7701 and SMMC-7721 cells were subjected to hypoxia culture.But the changes in SMMC-7721 were more significant than QSG-7701.The intracellular distribution of HMGB1 displayed dramatic translocation and HMGB1 protein in the cytoplasm was increased after SMMC-7721 cells were subjected to hypoxia cuhure for 12 h.SB203580,SP600125 and PD98059 showed partial inhibitory effects on hypoxia-induced HMGB1 release.Conclusion Hypoxia can induce HCC cells to release HMGB1,which mechanisms may involve in MAPK signal transduction pathways.
