腺苷类似物__(期刊论文)

腺苷类似物对肿瘤细胞的选择毒性效应

http://www.100md.com 《广东药学院学报》 2005年第2期

腺苷类似物,,腺苷类似物；细胞毒；IC50；细胞形态学；凋亡,1材料和方法,2结果,3讨论,参考文献

     摘要目的观察3种典型腺苷类似物对肿瘤细胞的毒性效应。方法以胎盼蓝活细胞拒染法测定药物对细胞生长、增殖的抑制及IC50 ；以流式细胞术(FCM)观察药物对细胞周期的影响；以荧光双染法(Hoechst33258/PI)观察药物对细胞形态学的影响；以Western blot法观察药物对细胞P53、Bcl2、Bax蛋白表达的影响。结果 2ClAdo、2CldAdo对所研究的细胞均有程度不等的毒性；2’dAdo对各细胞生长、增殖均无明显抑制(c=100 μmol/L即30 μg/mL内)；2CldAdo明显阻断细胞于S、G2/M期，2ClAdo阻断细胞于G0/G1期；2CldAdo 致细胞坏死为主，2ClAdo 既致细胞坏死又诱导凋亡；2ClAdo 下调Bcl2，上调P53、Bax蛋白表达；2CldAdo小幅上调P53、小幅下调Bcl2，不影响Bax蛋白表达。结论腺苷类似物对细胞生长、增殖呈选择性抑制，2ClAdo、2CldAdo对实体肿瘤细胞有程度不等的毒性，其毒性差异与凋亡相关因子P53、Bcl2、Bax介导有关。

    关键词腺苷类似物；细胞毒；IC50；细胞形态学；凋亡

    Selective cytotoxicity of three adenosine analogues on carcinoma cells

    ZHU Feng，LIU XinGuang，LIANG Nianci

    (1. Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang 524023, China; 2. Guangzhou Occupational Diseases Prevention & Treatment Center, Guangzhou 510620, China)

    Abstract Objective To study the cytotoxicity of three adenosine analogues on different carcinoma cells. Methods Trypan blue dye exclusion assay was utilized to observe the effects of adenosine analogues on cell growth and proliferation. Flow cytometry was used to measure the cells cycle kinetics of the treated cells. Hoechst33258/PI double staining was performed to evaluate the cell morphology. Western blotting was conducted to analyze the expressions of p53, Bcl2 and Bax. Results 2ClAdo and 2CldAdo had different cytotoxicities on the cells, while 2’dAdo had no cytotoxicity on the cells. 2CldAdo blocked the cell growth at the phase of S and G2/M, while 2ClAdo at the phase of G0/G1. 2CldAdo mainly induced cell necrosis, while 2ClAdo induced both cell necrosis and apoptosis. Downregulated Bcl2 expression and upregulated p53 and Bax expression were associated with 2ClAdo, while 2CldAdo downregulated Bcl2 expression and upregulated mildly p53 expression without any effect on Bax expression.Conclusions Adenosine analogues selectively inhibit cell growth and proliferation. 2ClAdo and 2CldAdo have different cytotoxicities on carcinoma cells, which associated with some apoptosisrelated factors such as p53, Bcl2 and Bax. ......

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