CDP抑制乳腺癌细胞T47D生长及逆转p16基因甲基化的研究

被引：2

作者：

徐丹

覃扬

孙芝琳

孙泽芳

机构：

[1] 四川大学华西基础医学与法医学院生物化学与分子生物学教研室,四川大学华西基础医学与法医学院生物化学与分子生物学教研室,四川大学华西基础医学与法医学院生物化学与分子生物学教研室,四川大学华西基础医学与法医学院生物化学与分子生物学教研室成都,成都,成都,成都

来源：

四川大学学报(医学版) | 2004年 / 06期

关键词：

CDP; 5-氮杂胞苷; 乳腺癌; p16基因; 甲基化特异性PCR;

D O I：

暂无

中图分类号：

R737.9 [乳腺肿瘤];

学科分类号：

摘要：

目的　研究 CDP(一种中药成分 )抑制乳腺癌 T4 7D细胞株生长的机制。方法　不同浓度的 5 -氮杂胞苷 (5 - azacytidine,5 - aza- CR)或 CDP与 T4 7D细胞培养数天 ,细胞增殖试验 (MTT法 )检测对 T4 7D细胞生长的影响 ;流式细胞术检测凋亡峰和细胞周期改变 ;甲基化特异性 PCR(MSP)检测用药前后 p16基因甲基化、非甲基化状态及程度的改变。结果　 5 - aza- CR和 CDP均对细胞生长呈浓度和时间依赖性抑制作用 (P<0 .0 5 ) ;在试验药物浓度 5 - aza- CR2 μm ol/ L,CDP5 0 μm ol/ L 的作用下 ,对细胞生长周期有影响 :G0 / G1 期细胞数由 6 5 .1%增加到71.3%和 84 .3% ,S期细胞数由 19.4 %减少到 14 .3%和 7.2 % ;药物作用细胞 6 d后对 p16基因有完全去甲基化作用。结论　 CDP可以逆转 p16基因高甲基化 ,并可能因此抑制肿瘤细胞生长。

引用

页码：792 / 796

页数：5

共 12 条

[1]

Effects of sinefungin and Sadenosylhomo cysteine on DNA and protein methyltransferases from Streptomyces and other bacteria. Barbes C,Sanchez J,Yebra MJ. FEMS Microbiology Immunology . 1990

[2]

Changes in DNA methylation in neoplasia: pathophysiology and therapertic implications. Valeria Santini,Hagop M,Kantarjian. Annals of Internal Medicine . 2001

[3]

Hypermethylation of the CpG island of Ras association domain family 1A (RASSF1A),a putative tumor suppressor gene from the 3p21. 3 locus, occurs in a large percentage of human breast cancers. Dammann R,Yang G,Pfeifer GP. Cancer Research . 2001

[4]

A Radical-BasedStrategy for theSynthesis ofHigherHomologues ofSinefungin. EdmilsonJoséMaria,AdilsonDavid daSilva,Jean-L ouisFourrey. EuropeanJournal ofOrganicChemistry . 2000

[5]

Toxicity of 5-aza-2 ’ -deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Juttermann R,Li E,Jaenisch R. Proceedings of the National Academy of Sciences of the United States of America . 1994

[6]

Methylation-specific PCR, a novol PCR assay for methylation status of CpG islands. Herman JG,Graff JR,Myohanen S. Proceedings of the National Academy of Sciences of the United States of America . 1996

[7]

Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors. Dominguez G,Silva J,Garcia JM. Mutation Research . 2003

[8]

Mechanism of extracellular ATP-and adenosine-induced apoptosis of cultured pulmonary artery endothelial cells. Sharon Rounds,Winnie Lin Yee,Doloretta D. American Journal of Physiology Lung Cellular and Molecular Physiology . 1998

[9]

5-aza-2‘- deoxycytidine induces retinoic acid receptor beta 2 demethylation , cell cycle arrest and growth inhibition in breast carcinoma cells. Yang Q,Shan L,Yoshimura G,Nakamura M,Nakamura Y,Suzuma T,Umemura T,Mori I,Sakurai T,Kakudo K. Anticancer Research . 2002

[10]

5-Azacytidine treatment of the fission yeast leads to cytotoxicity and cell cycle arrest. Taylor EM,McFarlane RJ,Price C. Molecular and General Genetics . 1996

← 1 2 →