Svechnikova Irina, Almqvist Per M, Ekström Tomas J
Department of Woman and Child Health, Karolinska Institutet, Pediatric Endocrinology Unit, Q2:08, Karolinska University and Hospital, S-171 76 Stockholm, Sweden.
Int J Oncol. 2008 Apr;32(4):821-7.
The anti-neoplastic effects of histone deacetylase inhibitors (HDACi), Trichostatin A (TSA) and 4-phenylbutyrate (4-PB) on the human glioblastoma cell lines GBM-29, U-343 MG and U-343 MGa Cl. 2:6 were investigated. TSA and 4-PB induced apoptosis in the three cell lines in a dose- and time-dependent manner. Whereas caspase-3 activation was detected in all three cell lines, U-343 MG cells were more sensitive to the apoptotic effect of HDACi compared with U-343 MGa Cl. 2:6. TSA and 4-PB induced differentiation in the three cell lines, each cell line developing unique phenotypic characteristics. During long-term treatment with a low dose of HDACi U-343 MGa Cl. 2:6 cells developed an astrocytic morphology with expression of glial fibrillary acidic protein (GFAP). GFAP-negative U-343 MG cells changed their morphology in response to HDACi and down-regulated their expression of vimentin. The nestin and vimentin positive GBM-29 cells also showed a morphological differentiation, while the expression of the two malignancy markers decreased. In summary, our results showed that these three glioblastoma cell lines display unique phenotypes and differentiation patterns in response to HDACi.
研究了组蛋白脱乙酰酶抑制剂（HDACi）曲古抑菌素A（TSA）和4-苯丁酸（4-PB）对人胶质母细胞瘤细胞系GBM-29、U-343 MG和U-343 MGa Cl. 2:6的抗肿瘤作用。TSA和4-PB以剂量和时间依赖性方式诱导这三种细胞系凋亡。虽然在所有三种细胞系中均检测到半胱天冬酶-3激活，但与U-343 MGa Cl. 2:6相比，U-343 MG细胞对HDACi的凋亡作用更敏感。TSA和4-PB诱导这三种细胞系分化，每个细胞系呈现出独特的表型特征。在用低剂量HDACi长期处理期间，U-343 MGa Cl. 2:6细胞呈现出星形胶质细胞形态，并表达胶质纤维酸性蛋白（GFAP）。GFAP阴性的U-343 MG细胞对HDACi作出反应，改变其形态并下调波形蛋白的表达。巢蛋白和波形蛋白阳性的GBM-29细胞也表现出形态分化，而这两种恶性标志物的表达降低。总之，我们的结果表明，这三种胶质母细胞瘤细胞系在对HDACi的反应中呈现出独特的表型和分化模式。
