Alterations in gene expression profiles correlated with cisplatin cytotoxicity in the glioma U343 cell line

被引:13
作者
Carminati, Patricia Oliveira [2 ]
Mello, Stephano Spano [2 ]
Fachin, Ana Lucia [2 ]
Junta, Cristina Moraes [2 ]
Sandrin-Garcia, Paula [2 ]
Carlotti, Carlos Gilberto [3 ]
Donadi, Eduardo Antonio [4 ]
Silva Passos, Geraldo Aleixo [2 ,5 ]
Sakamoto-Hojo, Elza Tiemi [1 ,2 ]
机构
[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Biol, BR-14040901 Ribeirao Preto, SP, Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, BR-14040901 Ribeirao Preto, SP, Brazil
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cirugia & Anat, BR-14040901 Ribeirao Preto, SP, Brazil
[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, BR-14040901 Ribeirao Preto, SP, Brazil
[5] Univ Sao Paulo, Fac Odontol Ribeirao Preto, BR-14040901 Ribeirao Preto, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
apoptosis; cisplatin; gene expression; glioma; GLIOBLASTOMA CELLS; TUMOR-SUPPRESSOR; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; MICROARRAY DATA; OVARIAN-CANCER; BRAIN-TUMORS; CYCLE ARREST; IN-VIVO; APOPTOSIS;
D O I
10.1590/S1415-47572010005000013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Gliomas are the most common tumors in the central nervous system, the average survival time of patients with glioblastoma multiforme being about 1 year from diagnosis, in spite of harsh therapy. Aiming to study the transcriptional profiles displayed by glioma cells undergoing cisplatin treatment, gene expression analysis was performed by the cDNA microarray method. Cell survival and apoptosis induction following treatment were also evaluated. Drug concentrations of 12.5 to 300 mu M caused a pronounced reduction in cell survival rates five days after treatment, whereas concentrations higher than 25 mu M were effective in reducing the survival rates to similar to 1%. However, the maximum apoptosis frequency was 20.4% for 25 mu M cisplatin in cells analyzed at 72 h, indicating that apoptosis is not the only kind of cell death induced by cisplatin. An analysis of gene expression revealed 67 significantly (FDR < 0.05) modulated genes: 29 of which down- and 38 up-regulated. These genes belong to several classes (metabolism, protein localization, cell proliferation, apoptosis, adhesion, stress response, cell cycle and DNA repair) that may represent several affected cell processes under the influence of cisplatin treatment. The expression pattern of three genes (RHOA, LIMK2 and TIMP2) was confirmed by the real time PCR method.
引用
收藏
页码:159 / 168
页数:10
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