阿糖胞苷诱导肺腺癌细胞凋亡与p73激活相关(英文) 被引量：1

p73 activation is involved in regulation of Ara-C-induced apoptosis in human lung adenocarcinoma cells

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摘要目的体外观察阿糖胞苷(1-β-D-arabinofuranosylcytosine,Ara-C)对肺腺癌A549细胞凋亡的诱导作用,探讨p53、p73基因在此凋亡过程中的调控作用。方法 Ara-C体外作用于A549细胞,TUNEL法检测A549细胞的凋亡;透射电镜观察A549细胞凋亡的典型超微结构;免疫印迹法检测Ara-C诱导A549细胞凋亡过程中p53、p73是否起到了凋亡调控的作用。结果 1.Ara-C作用A549细胞的实验组检测到大量的TUNEL阳性反应细胞,统计学分析实验组凋亡率与对照组相比有极显著性差异(P<0.01);2.透射电镜观察到凋亡小体等典型的超微结构;3.免疫印迹法显示,Ara-C诱导A549细胞凋亡中p53蛋白表达量无变化,而p73蛋白表达量随A549细胞凋亡程度的增强而增加。结论 Ara-C明显诱导肺腺癌A549细胞凋亡而并非依赖于p53的调控作用;p73可能在Ara-C诱导A549细胞凋亡过程中发挥重要作用。 Objective To study the apoptosis pathway of human lung adenocarcinoma cell line A549 induced by 1- β-D-arabinofuranosylcytosine （Ara-C） in vitro. Methods A549 cells were incubated with Ara-C for 72hours in vitro. Biological changes of apoptotie cells were studied by TUNEL staining. Morphological changes of the A549 cells treated with Ara-C were observed by transmission electron microscope. The expressions of p53 and p73 were investigated by Western blotting. Results 1. Apoptotic rates of A549 cells exposure to Ara-C studied by TUNEL staining were higher than that of the control （P 〈 0. 01 ）. 2. Apoptosis body was apparently observed by transmission electron microscope. 3. Endogenous p73 but not p53 was induced and activated in dose-dependent manner upon Ara-C treatment by Western blotting. Conclusion Ara-C can effectively induce apoptosis of A549 cells. DNA damage-induced apoptosis of A549 cells treated by Ara-C is independent of functional p53. Up-regulation of p73 may play an important role that enhances the sensitivity of A549 cells to Ara-C and be partly responsible for p53-independent apoptosis.

作者张露刘宁吕丹瑜马万云李英

机构地区北京大学基础医学院人体解剖学与组织学胚胎学系清华大学物理系原子分子纳米科学教育部重点实验室

出处《解剖学报》 CAS CSCD 北大核心 2011年第1期50-53,共4页 Acta Anatomica Sinica

基金 National natural science foundation of China(90919012)

关键词阿糖胞苷 P73 p53 A549细胞 TUNEL法透射电镜免疫印迹法 Cytarabine p73 p53 A549 cells TUNEL staining Transmission electron microscopy Western

分类号 R73-36 [医药卫生—肿瘤]

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参考文献18

1Jemal A,Siegel R,Ward E,et al.Cancer statistics,2009[J].CA Cancer J Clin,2009,59(4):225-249.
2Stinchcombe TE,Socinski MA.Current treatments for advanced stage non-small cell lung cancer[J].Proc Am Thorac Soc,2009,6(2):233-241.
3Hammerschmidt S,Wirtz H.Lung cancer:current diagnosis and treatment[J].Dtsch Arztebl Int,2009,106(49):809-820.
4Lee H,Tosh DK,Choi WJ,et al.Synthesis and antitumor activity of 1-beta-4-selenoarabinofuranosyl cytosine (4'-seleno-ara-C)[J].Nucleic Acids Symp Ser,2008,52(1):639-640.
5Ailenberg M,Goldenberg NM,Silverman M.Description of a PCR-based technique for DNA splicing and mutagenesis by producing 5' overhangs with run through stop DNA synthesis utilizing Ara-C[J].BMC Biotechnol,2005,5:23-28.
6Kripp M,Hofheinz RD.Treatment of lymphomatous and leukemic meningitis with liposomal encapsulated cytarabine[J].Int J Nanomedicine,2008,3(4):397-401.
7De Vries JF,Falkenburg JH,Willemze R,et al.The mechanisms of Ara-C-induced apoptosis of resting B-chronic lymphocytic leukemia cells[J].Haematologica,2006,91(7):912-919.
8Levrero M,De Laurenzi V,Costanzo A,et al.The p53/p63/p73 family of transcription factors:overlapping and distinct functions[J].J Cell Sci,2000,113:1661-1670.
9Hu Yingchuan,McDermott MP,Ahrendt SA.The p53 codon 72 proline allele is associated with p53 gene mutations in non-small cell lung cancer[J].Clin Cancer Res,2005,11(7):2502-2509.
10Paik KH,Park YH,Ryoo BY,et al.Prognostic value of immunohistochemical staining of p53,bcl-2,and Ki-67 in small cell lung cancer[J].J Korean Med Sci,2006,21:35-39.

二级参考文献14

1Rapp E PJ,Willan A,Cormier Y,et al.Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer-report of a Canadian multicenter randomized trial[J].Journal Clinical Oncology,1988,16(4):633-641.
2Grilli R OA,Julian JA.Chemotherapy for advanced non-small-cell lung cancer:how much benefit is enough[J] ? J Clin Oncol,1993:11 (10):1866-1872.
3Kufe DW GJ,Spriggs DR.Cellular and clinical pharmacology of lowdose Ara-C[J].Semin Oncol,1985,12 (2):200-207.
4Gandhi WPaV.Cellular pharmacodynamics of anticancer druges[J].Semin Oncol,1993,20(1):50-63.
5Markman M HT,Reichman B,Hoskins W,et al.Intraperitoneal cytosine arabinoside therapy in ovarian carcinoma[J].J Clin Oncol,1999,9(2):204-210.
6Wang LM WJ,Capizzi RL.The effect of Ara-C-induced inhibition of DNA synthesis on its cellular pharmacology[J].Cancer Chemother Pharmacol,1990,25(6):418-424.
7Tommer Ravid RA,Sylvie PC,Jerry R,et al.Impaired regulation of 3 hydroxy-3-methylglutary1 -coenzyme a reductase degradation in lovastatin-resistant cells[J].J Biol Chem,1999,274 (41):29341-29351.
8Syu-ichi Kanno,AH,Yurie W,et al.Susceptibility to cytosine arabinoside (Ara-C)-induced cytotoxicity in human leukemia cell lines[J].Toxicology Letters,2004,152(2):149-158.
9Kroemer KFFG.Organelle-specific initiation of cell death pathways[J].Nat Cell Biol,2001,3 (11):E255-263.
10Strasser A OCL,Dixit VM.Apoptosis signaling[J].Annu Rev Biochem,2000,69 (1):217-245.