Effect of antineoplastic drugs on the expression of Bcl-2 and Bcl-xL genes in the feline T-cell leukemia cell line

Effect of antineoplastic drugs on the expression of Bcl-2 and Bcl-xL genes in the feline T-cell leukemia cell line
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DOI:
10.1016/j.rvsc.2005.03.001
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发表时间:
2005-12-01
影响因子:
2.4
通讯作者:
Hasegawa, A
Hasegawa, A
中科院分区:
农林科学3区
文献类型:
--
作者:
Sano, J;Nagafuchi, S;Hasegawa, A

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Bcl-2基因是一个迅速扩大的调节细胞凋亡的基因家族的第一个成员。Bcl-2已被证明可以抑制多种刺激(包括化疗和γ辐照)引发的细胞死亡。猫淋巴瘤的化疗通常使用抗肿瘤药物,据报道抗肿瘤药物可诱导肿瘤细胞凋亡。然而,化疗药物对猫肿瘤诱导的精确凋亡信号尚未完全表征。因此,我们评估了这些药物在体外治疗FT-1后Bcl-2和Bcl-xL的表达。本研究对猫Bcl-xL基因全长进行了测序,并研究了Bcl-2和Bcl-xL mrna在阿霉素、强的松龙和长春新碱培养的猫淋巴瘤细胞株FT-1中的表达情况。猫Bcl-xL克隆全长1163个碱基对,编码233个氨基酸。预测的氨基酸序列与狗、人、小鼠、猪、大鼠和羊的Bcl-xL序列同源性分别为99.1%、98.7%、96.1%、97.4%、97.0%和97.9%。在多柔比星(0.3 μ g/ml)、强的松龙(0.2 μ g/ml)和长春新碱(5 ng/ml)刺激的FT-1中,Bcl-2转录物水平在孵育24 h时分别增加到未刺激FT-1的约41.0倍、62.0倍和11.1倍。另一方面,多柔比星和强的松龙刺激FT-1培养24 h时,Bcl-xL转录本水平较对照组显著提高了4.2倍和5.8倍,长春新碱诱导的Bcl-xL水平降低了0.35倍。(c) 2005 Elsevier Ltd版权所有。
The Bcl-2 gene is the first member of a rapidly expanding family of genes that regulate apoptosis. Bcl-2 has been shown to repress cell death triggered by a diverse array of stimuli including chemotherapy and gamma-irradiation. Chemotherapy of feline lymphoma is generally carried out with antineoplastic drugs, which are reported to induce apoptosis in tumor cells. However, the precise apoptotic signals, induced by chemotherapeutic drugs against feline tumors have not been fully characterized. Therefore, we have evaluated the expression of Bcl-2 and Bcl-xL in FT-1 upon in vitro treatment with these drugs.In the present study, full length of feline Bcl-xL gene was sequenced, and the expressions of Bcl-2 and Bcl-xL mRNAs in feline lymphoma cell line (FT-1) cultured with doxorubicin, prednisolone or vincristine were investigated. Feline Bcl-xL clone was 1163 base pairs in length and encoded 233 amino acids. The predicted amino acid sequence was 99.1%, 98.7%, 96.1%, 97.4%, 97.0% and 97.9% homologous to predicted Bcl-xL of dog, human, mouse, pig, rat and sheep, respectively.The levels of Bcl-2 transcripts at 24 h incubation in FT-1 stimulated with doxorubicin (0.3 mu g/ml), prednisolone (0.2 mu g/ml) and vincristine (5 ng/ml) were increased to about 41.0-, 62.0- and 11.1-fold to those in non-stimulated FT-1, respectively. Oil the other hand, the level of Bcl-xL transcripts at 24 h incubation in FT-1 stimulated by doxorubicin and prednisolone were significantly increased about 4.2- and 5.8-folds to the controls and inducible level of Bcl-xL by vincristine was decreased about 0.35-folds. (c) 2005 Elsevier Ltd. All rights reserved.