吉西他滨治疗实验性C6胶质瘤：对细胞周期和凋亡率的影响。

Gemcitabine treatment of experimental C6 glioma: the effects on cell cycle and apoptotic rate.

作者信息

Carpinelli Giulia, Bucci Barbara, D'Agnano Igea, Canese Rossella, Caroli Fabrizio, Raus Laura, Brunetti Ercole, Giannarelli Diana, Podo Franca, Carapella Carmine M

机构信息

Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy.

出版信息

Anticancer Res. 2006 Jul-Aug;26(4B):3017-24.

PMID:16886629

Abstract

Gemcitabine (dFdCyd) is a deoxycytidine analogue showing a broad spectrum of cytotoxic activity; additionally, at non-cytotoxic concentrations, it is a potent radiosensitiser. Its in vitro and in vivo effects were studied on C6 rat glioma. In vitro, dFdCyd induced an increase in S-phase cells at the end of treatment, with a reduction in G1 and G2 cell cycle-phase cells and relevant effects on the apoptotic rate. The in vivo effects of dFdCyd were studied on rats bearing intracranial C6 glioma. The drug was administered at a dose of 120 mg/Kg every 3 days x 4 doses. A significant effect on tumour growth was detected by longitudinal MRI analyses. Furthermore, the drug induced an inhibitory effect on tumour growth, 72 h after a 300 mg/Kg single dose. Analyses performed on tumour specimens showed relevant G1-phase accumulation and about 45% apoptotic cells. The present results justify further studies to determine the potential efficacy of dFdCyd in the treatment of malignant gliomas.

摘要

吉西他滨（2′,2′-二氟脱氧胞苷）是一种脱氧胞苷类似物，具有广泛的细胞毒活性；此外，在非细胞毒浓度下，它还是一种有效的放射增敏剂。对C6大鼠胶质瘤研究了其体内外效应。在体外，2′,2′-二氟脱氧胞苷在处理结束时诱导S期细胞增加，G1期和G2期细胞周期细胞减少，并对凋亡率产生相关影响。对颅内接种C6胶质瘤的大鼠研究了2′,2′-二氟脱氧胞苷的体内效应。每3天以120 mg/Kg的剂量给药，共4剂。通过纵向MRI分析检测到对肿瘤生长有显著影响。此外，单次300 mg/Kg剂量给药72小时后，该药物对肿瘤生长产生抑制作用。对肿瘤标本进行的分析显示有明显的G1期蓄积和大约45%的凋亡细胞。目前的结果证明有必要进一步研究以确定2′,2′-二氟脱氧胞苷在治疗恶性胶质瘤方面的潜在疗效。