Apoptosis of human glioma cells in vitro and in vivo induced by a neutralizing antibody against human basic fibroblast growth factor.
Apoptosis of human glioma cells in vitro and in vivo induced by a neutralizing antibody against human basic fibroblast growth factor.
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DOI：
10.3171/jns.1996.85.6.1072
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发表时间：
1996-12
影响因子：
4.1
通讯作者：
N. Murai;T. Ueba;J. Takahashi;H. Yang;H. Kikuchi;H. Hiai;Masakazu Hatanaka;M. Fukumoto
中科院分区：
文献类型：
--
作者：
N. Murai;T. Ueba;J. Takahashi;H. Yang;H. Kikuchi;H. Hiai;Masakazu Hatanaka;M. Fukumoto
碱性成纤维细胞生长因子（bFGF）是神经外胚层和中胚层衍生细胞的有丝分裂因子，是一种有效的血管生成因子。在人类胶质瘤组织和细胞中检测到大量的bFGF及其受体，胶质瘤中的bFGF被认为是一种自分泌生长因子，参与了细胞的自主生长。一种针对bFGF的中和性小鼠单克隆抗体（MAb） 3H3 MAb已被证明可以抑制人胶质瘤细胞系的体外和体内生长。本研究表明，高表达bFGF及其受体的人胶质瘤细胞系U-87MG和U-251MG在3H3 MAb培养下可诱导细胞凋亡。同时也证实3H3 MAb能引起移植到裸鼠体内的同种胶质瘤细胞的凋亡。此外，通过基因转染强制bcl-2蛋白过表达可阻止3H3单克隆抗体诱导的胶质瘤细胞凋亡。因此，利用中和抗体诱导细胞凋亡是一种很有前途的治疗胶质瘤的方法。
Basic fibroblast growth factor (bFGF) is mitogenic to neuroectoderm- and mesoderm-derived cells and is a potent angiogenic factor. Abundant amounts of this factor and its receptor are detected in human glioma tissues and cells, and bFGF in glioma is thought to be involved in autonomous cell growth as an autocrine growth factor. A neutralizing mouse monoclonal antibody (MAb) against bFGF, 3H3 MAb, has been shown to inhibit both in vitro and in vivo growth of human glioma cell lines. This study shows that the human glioma cell lines U-87MG and U-251MG, which express high levels of bFGF and its receptor, can be induced to undergo apoptosis when cultured with 3H3 MAb. It is also demonstrated that 3H3 MAb can cause apoptosis in the same glioma cells that were transplanted into nude mice. Furthermore, enforced overexpression of bcl-2 protein by gene transfection prevented 3H3 MAb-induced apoptosis of glioma cells. It is concluded that induction of apoptosis by the neutralizing antibody is a promising therapeutic strategy for glioma.