3 讨论
3.1 视网膜母细胞瘤HXO-Rb44细胞的分化
视网膜母细胞瘤是一种有分化潜力的干细胞,在不同因素的作用下,视网膜母细胞瘤可向视网膜的视锥及视杆细胞、色素上皮细胞和M%26uuml;llers胶质细胞方向分化[1]。NSE可作为神经元分化的特异性标志。易玉珍等人[6]报道视网膜母细胞瘤细胞主要向神经细胞方向分化,Fassina等人[1]的研究结果表明,8-Br-cAMP可提高视网膜母细胞瘤Y-79细胞株表达NSE,促进该细胞向神经细胞方向分化。本实验观察到HXO-Rb44细胞经8-Br-cAMP处理后呈现神经样突起并提高作为神经元分化特异性标志的NSE的表达,表明8-Br-cAMP可促使人HXO-Rb44细胞向神经细胞方向分化。
3.2 NO在8-Br-cAMP对视网膜母细胞瘤HXO-Rb44细胞分化和凋亡中的作用
NO及NOS广泛存在于神经元,有报道[11]NO作为细胞的信息分子具有多种功能,如舒张血管、提高巨噬细胞免疫功能和有利于中枢及外周神经系统间的神经传递作用,NO不但参与神经递质释放、神经发育、突触的形成以及基因表达的调节,而且在细胞的分化和凋亡中起重要作用。Shami等人[12]报道,NO可抑制急性非淋巴细胞白血病的生长,诱导其分化和调节其基因的表达。Ogura等人[13]发现在分化的神经母细胞瘤TGW细胞株内神经元NOS活性和NOS mRNA表达均增高。Xie等[14]报道NO可诱导K-1735黑色瘤细胞的凋亡与Bcl-2基因的下调有关,而Bcl-2是调控细胞凋亡的重要基因[9],其产物能抑制细胞凋亡。Chen等人[15]也报道,cAMP类似物,如8-Br-cAMP,DB-cAMP等具有抑制恶性胶质细胞瘤A-172细胞增殖、促进分化、诱导凋亡的作用。
本实验观察到,8-Br-cAMP可促进HXO-Rb44细胞产生NO,增加NOS酶活性及NOS的基因表达,降低Bcl-2mRNA的基因表达,表明NO的产生是受其相应基因及酶控制的,在8-Br-cAMP诱导HXO-Rb44细胞的分化和凋亡过程中,NO可能起了关键作用。
本文受河南省科委攻关课题资助(课题编号:971200261)
参考文献:
1.Fassina G,Aluigi MG,Gentleman S,et al.The cAMP analog 8-Cl-cAMP inhibits growth and induces differentiation and apoptosis in retinoblastoma cells.Int J Cancer,1997,72∶ 1088
2.Nork TM,Schwartz TL,Doshi HM,et al.Retionblastoma cell of origin.Arch Ophthalmol,1995,113∶ 791
3.方家椿,石永进,彭敬,等.8-Cl-cAMP及其新生物对HL-60细胞生长抑制和分化诱导作用的初步研究.中华肿瘤杂志,1993,15∶ 141
4.Li H,Chen HC,Huang FL,et al.Identification of rapidly dephosphorylating 95-Kda protein as elongation factor 2 during 8-Br-cAMP treatment of NIE 11s neuroblastoma cells.Biochen-biophys Res Commun,1995,217∶ 131
5.Bosanquet AG,Burlton AR,Bell PB,et al.Ex vivo cytotoxic during evaluation by DiSC assary to expedite identification of clinical targets:results with 8-chloro-cAMP.Br J Cancer,1997,76∶ 511
6.易玉珍,杨为中,郑湖玲.视网膜母细胞瘤的细胞来源与分化研究.中华眼科杂志,1994,30∶ 214
7.Fresno M.The role of tumor necrosis factor,interleukin 6,interferon-gamma and inducible nitric oxide synthase in the development and pathology of nervous system.Pro Neurobiol,1998,56∶ 307
8.Ghigo D,Priotto C,Migliorino D,et al.Retinoic acid-induced differentiation in a human neuroblastoma cell line is associated with an increase in nitric oxide synthesis.J Cell Physiol,1998,174∶ 99
9.石林祥,综述.Bcl-2基因与乳腺癌发生发展的相关性.肿瘤,1998,18(5)∶ 367
10.邓新国,吴景兰,王翔,等.8-Br-cAMP对人视网膜母细胞瘤HXO-Rb44 细胞癌基因的表达效应.眼科研究,1999,17(4)∶ 241
11.Yun HY,Dawson VL,Dawson TM.Neurobiology of nitric oxide.Crit Rev Neurobiol,1996,10∶ 291
12.Shami PJ,Sauls DL,Weinberg JB.Schedule and concentration-dependent induction of apoptosis in leukemia cells by nitric oxide.Leukemia,1998,12∶ 1461
13.Ogura T,Nakayama K,Fujisawa H and Esumi H.Neuronal nitric oxide synthase expression in neuronal cell differentiation.Neurosci Lett,1996,204∶ 89
14.Xie K,Wang Y,Huang S,et al.Nitric oxidemediated apoptosis of k-1735melanoma cells is associated with downregulation of Bcl-2.Oncogene,1997,15(7)∶ 771
15.Chen TC,Hinton DR,Zhidovetzki R,et al.Up-regulation of the cAMP/PKA pathway inhibits proliferation,induces differentiation,and leads to apoptosis in malignant gliomas.Lab Invest,1998,78∶ 165
收稿:1999-08-25
修回:2000-05-25 上一页 [1] [2] [3] |