【摘要】 背景与目的:腺苷作用于细胞信号转导系统,可抑制磷脂酰肌醇4-激酶活性、升高腺苷酸环化酶活性和细胞内cAMP水平、抑制血小板肌动蛋白聚合等。腺苷类似物有上述腺苷的生物活性,且不易为腺苷脱氨酶所降解,具有相对较长的生物半衰期。本研究拟观察2-氯腺苷、2-氯脱氧腺苷、2’-脱氧腺苷对人高转移卵巢癌细胞HO-8910PM体外侵袭的抑制作用。方法:以3种腺苷类似物处理HO-8910PM朱峰,等.三种腺苷类似物抑制人细胞、以5-氟尿嘧啶为细胞敏感对照,用台盼蓝拒染法观察药物对细胞的毒性效应;以人工重组基底膜观察细胞的侵袭、粘附和运动能力;以明胶酶显影法观察细胞基质金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)的分泌及活性;以RT-PCR检测细胞mta1mRNA、nm23H1mRNA表达。结果:2-氯腺苷和2-氯脱氧腺苷处理高转移卵巢癌细胞72h的IC50值分别为5.80μmol/L和2.61μmol/L,2’-脱氧腺苷对该细胞无明显抑制(对细胞的IC50值大于100μmol/L);6.0μmol/L的2-氯腺苷和2-氯脱氧腺苷对细胞侵袭的抑制率分别为(42.5±1.5)%(与对照组比较,P<0.01)和(9.9±0.5)%(P<0.05);对细胞运动的抑制率分别为(36.9±2.1)%(P<0.01)和(17.1±0.4)%(P<0.05);对细胞粘附的抑制率分别为(32.2±2.3)%(P<0.01)和(19.5±3.1)%(P<0.05)。而2’-脱氧腺?更多还原

【Abstract】 BACKGROUND &OBJECTIVE: Adenosine plays an essential role in cell s signal transduction, including inhibiting the activity of phosphatidylinositol 4 -kinase, up-regulating the activity of adenylate cyclase and the concentration of cAMP, and inhibiting platelet actin polymerization. Adenosine analogues have the same bioactivities as adenosine,but are slowly deaminated by adenosine deam inase. This study was to observe the effects of 2-chloro-adenosine(2-ClAdo) , 2-chloro-2-deoxyadenosine (2-CldAdo), and 2-deoxyadenosine (2-dAdo ) on invasion of human ovarian cancer cell line HO-8910PM. METHODS: HO-8910PM cells were treated with 2-ClAdo, 2-CldAdo, and 2-dAdo, Trypan blue dye excl usion assay was used to examine cytotoxities of these 3 adenosine analogues to H O-8910PM cells, 5-fluorouracil (5-FU) was used as sensitive control. Reconsti tuted basement membrane invasion assay was used to evaluate invasive,adhesive,an d kinetic activities of the cells. PAGE substrate zymography was used to analyze secretion,and activity of matrix metalloproteinase-9 (MMP-9). Reverse transcr iptase-polymerase chain reaction (RT-PCR) was used to analyze mRNA levels of m ta1 and nm23H1. RESULTS: The 50%inhibition concentrations (IC50) of 2-ClAdo, a nd 2-CldAdo at 72 h were 5.80, and 2.61 μmol/L; while inhibitory effect of 2 -dAdo on the cells was not significant, its IC50 was more than 100 μmol/L. Inh ibition rates of 6.0 μmol/L of 2-ClAdo, and 2-CldAdo on cells invasion were (42.5±1.5)%, and (9.9±0.5)%; those on cells migration were (36.9±2.1) %,and (17.1±0.4)%;and those on cells adhesion were (32.2±2.3)%, and (1 9.5±3.1)%. All these inhibition rates were significantly higher than those of control (P< 0.05). While 2-dAdo had no significant effect on cells invasio n. All 3 chemicals could not inhibit the production and activity of MMP-9 in HO -8910PM cells. 2-ClAdo down-regulated mRNA level of mta1, but neither 2-ClAd o nor 2-CldAdo affected mRNA level of nm23H1. CONCLUSION: Of these 3 adenosine analogues, 2-ClAdo might be a potential chemical inhibiting tumor invasion and metastasis because of its weaker cytotoxity but stronger inhibitive effect on in vasion of tumor cells.更多还原