Department of Neurosurgery, First Hospital of China Medical University, Heping District, Shenyang, Liaoning 110001, PR China.
Oncol Rep. 2012 Jul;28(1):155-60. doi: 10.3892/or.2012.1800. Epub 2012 May 4.
The anti-apoptotic gene, B-cell lymphoma-2 (Bcl-2), has been reported to be overexpressed in gliomas and is related to tumor prognosis, suggesting a potential therapeutic target. Additionally, recent studies have demonstrated the existence of brain glioma stem cells (BGSCs) which are tumorigenic, self-renewable and dominate the biological behavior of gliomas. Currently BGSCs are committed as a new target of glioma therapies. However, few studies have focused on the expression of Bcl-2 in BGSCs. We performed a series of experiments to culture BGSCs from eight clinical specimens, followed by real-time RT-PCR and immunoassays to compare the expression levels of Bcl-2 in BGSCs and their corresponding primary glioma cells (PGCs). The results showed that Bcl-2 mRNA and protein expression levels are higher in BGSCs compared to their counterparts, and the expression levels are related to glioma malignancies. As an anti-apoptotic gene, Bcl-2 assigns immortality characteristics to cells, which coincide with the pivotal biological feature of BGSCs. The experimental results indicated that BGSCs would evade apoptosis for higher Bcl-2 expression, and may interpret the drug resistance of glioma to cytotoxic drugs and other pro-apoptotic agents. New therapies targeting Bcl-2 must induce apoptosis in BGSCs, thus, resulting in treatment or even eradication of glioma.
抗凋亡基因 B 细胞淋巴瘤-2(Bcl-2)在神经胶质瘤中过度表达,并与肿瘤预后相关,提示其可能成为治疗靶点。此外,最近的研究表明存在脑胶质瘤干细胞(BGSCs),其具有致瘤性、自我更新能力,并主导神经胶质瘤的生物学行为。目前,BGSCs 被认为是神经胶质瘤治疗的新靶点。然而,目前少有研究关注 Bcl-2 在 BGSCs 中的表达。我们从 8 个临床标本中培养 BGSCs,并进行实时 RT-PCR 和免疫检测,以比较 BGSCs 及其相应的原代神经胶质瘤细胞(PGCs)中 Bcl-2 的表达水平。结果表明,与 PGCs 相比,BGSCs 中 Bcl-2 mRNA 和蛋白表达水平更高,且表达水平与神经胶质瘤恶性程度相关。作为一种抗凋亡基因,Bcl-2 赋予细胞永生特性,这与 BGSCs 的关键生物学特征相符。实验结果表明,由于更高的 Bcl-2 表达,BGSCs 会逃避凋亡,这可能解释了神经胶质瘤对细胞毒性药物和其他促凋亡药物的耐药性。针对 Bcl-2 的新疗法必须诱导 BGSCs 凋亡,从而实现对神经胶质瘤的治疗甚至根除。