CHARACTERIZATION AND CHEMOSENSITIVITY OF 2 CELL-LINES DERIVED FROM HUMAN GLIOBLASTOMAS
CHARACTERIZATION AND CHEMOSENSITIVITY OF 2 CELL-LINES DERIVED FROM HUMAN GLIOBLASTOMAS
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DOI：
10.1007/bf01050213
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发表时间：
1993-01-01
影响因子：
3.9
通讯作者：
KOWADA, M
中科院分区：
文献类型：
--
作者：
IZUMU, I;MINEURA, K;KOWADA, M
我们鉴定了两种人类胶质母细胞瘤细胞系，分别被命名为YH细胞和AM细胞。两株细胞系均保持原代培养时的形态，免疫组织化学表达胶质原纤维酸性蛋白（GFAP）和S-100蛋白。在指数培养阶段，YH细胞和AM细胞的群体倍增时间分别为30小时和25小时。AM细胞接种胸腺裸鼠形成大肿瘤的发生率高。与对氯乙基亚硝基脲的化学敏感性一样，在体外培养的细胞和手术获得的肿瘤标本中测量了o -6-甲基鸟嘌呤- dna甲基转移酶（MGMT）的活性。3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）检测显示YH细胞MGMT活性为1196 fmol/mg，对1-（4-氨基-2-甲基-5-嘧啶基）甲基-3-（2-氯乙基）-3-亚硝基脲盐酸盐（ACNU）具有耐药性。YH肿瘤标本MGMT活性为301 fmol/mg，在临床评价中反映ACNU化疗效果较差。AM细胞MGMT活性极低，仅为16 fmol/mg，易受ACNU的影响。而AM细胞的原始肿瘤标本表达628 fmol/mg的高值。考虑到ACNU化疗在两例患者中均无效，原肿瘤MGMT活性与ACNU的反应性有关。体外细胞系和各自肿瘤标本之间MGMT活性的差异来自acnu敏感鳗鱼的选择或长期培养过程中生物学特性的改变。这些结果表明，来源于人类脑肿瘤的细胞系是了解人类恶性胶质瘤的化学敏感性和建立相关化学敏感性试验的有用靶点。
We have characterized two human glioblastoma cell lines, which were designated as YH cells and AM cells. The two cell lines maintained morphological appearance observed in the primary culture and immunohistochemically expressed glial fibrillary acidic protein (GFAP) and S-100 protein. Population doubling time for YH cells and AM cells indicated 30 hours and 25 hours, respectively, in an exponential phase of culture. Inoculation of AM cells into athymic nude mice formed large tumors at a high incidence. As with chemosensitivity to chloroethylnitrosourea, O-6-methylguanine-DNA methyltransferase (MGMT) activity was measured in in vitro cultured cells as well as tumor specimens obtained at surgery. YH cells showed a high MGMT activity of 1196 fmol/mg and drug resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-cloroethyl)-3-nitrosourea hydrochloride (ACNU) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. YH tumor specimens indicated an MGMT activity of 301 fmol/mg, which reflected poor effectiveness of ACNU chemotherapy in the clinical evaluation. AM cells had an extremely low MGMT activity of 16 fmol/mg and were vulnerable to ACNU. Original tumor specimens of AM cells however expressed a high value of 628 fmol/mg. Considering that ACNU chemotherapy was not effective in the both patients, an MGMT activity of original tumors related with responsiveness to ACNU. Discrepancy in an MGMT activity between the in vitro cell lines and the respective tumor specimens comes from selection of ACNU-sensitive eels or alteration in biological characteristics during long term culture. These results suggest that cell lines derived human brain tumors are useful targets for understanding the chemosensitivity of human malignant gliomas and for establishing a pertinent chemosensitivity test.