Dexamethasone protected human glioblastoma U87MG cells from temozolomide induced apoptosis by maintaining Bax:Bcl-2 ratio and preventing proteolytic activities.
Dexamethasone protected human glioblastoma U87MG cells from temozolomide induced apoptosis by maintaining Bax:Bcl-2 ratio and preventing proteolytic activities.
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DOI：
10.1186/1476-4598-3-36
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发表时间：
2004-12-08
期刊：
影响因子：
37.3
通讯作者：
Ray SK
中科院分区：
文献类型：
--
作者：
Das A;Banik NL;Patel SJ;Ray SK
胶质母细胞瘤是最致命和最普遍的脑肿瘤。地塞米松（DXM）是一种常用的类固醇，用于治疗胶质母细胞瘤患者，在化疗药物治疗前缓解血管源性水肿和疼痛。替莫唑胺（TMZ），一种烷化剂，最近已被引入临床试验用于治疗胶质母细胞瘤。在这里，我们评估了DXM对TMZ诱导的人胶质母细胞瘤U87 MG细胞凋亡的调节作用。用不同剂量的DXM或TMZ处理新鲜生长的细胞6小时，然后在无药物培养基中孵育48小时。瑞氏染色和ApopTag法显示40 μM DXM处理的细胞无凋亡，而100 μM TMZ处理的细胞有大量凋亡。TMZ处理的细胞中的凋亡与细胞内游离[Ca 2 +]的增加相关，如通过Fura-2测定所确定的。蛋白质印迹分析显示Bax（促凋亡）和Bcl-2（抗凋亡）蛋白水平的改变，导致TMZ处理的细胞中Bax：Bcl-2比率增加。Western印迹分析还检测到钙蛋白酶和半胱天冬酶-3的过表达，其在特定位点切割270 kD α-血影蛋白，分别产生145和120 kD血影蛋白分解产物（SBDP）。然而，40 μM DXM预处理细胞1小时显著降低TMZ诱导的凋亡，降低Bax：Bcl-2比值和SBDP。我们的研究结果显示，DXM对TMZ诱导的人胶质母细胞瘤U87 MG细胞凋亡具有拮抗作用，这意味着在TMZ化疗前用DXM治疗胶质母细胞瘤患者可能会导致不良的临床结果。
Glioblastoma is the deadliest and most prevalent brain tumor. Dexamethasone (DXM) is a commonly used steroid for treating glioblastoma patients for alleviation of vasogenic edema and pain prior to treatment with chemotherapeutic drugs. Temozolomide (TMZ), an alkylating agent, has recently been introduced in clinical trials for treating glioblastoma. Here, we evaluated the modulatory effect of DXM on TMZ induced apoptosis in human glioblastoma U87MG cells. Freshly grown cells were treated with different doses of DXM or TMZ for 6 h followed by incubation in a drug-free medium for 48 h. Wright staining and ApopTag assay showed no apoptosis in cells treated with 40 μM DXM but considerable amounts of apoptosis in cells treated with 100 μM TMZ. Apoptosis in TMZ treated cells was associated with an increase in intracellular free [Ca2+], as determined by fura-2 assay. Western blot analyses showed alternations in the levels of Bax (pro-apoptotic) and Bcl-2 (anti-apoptotic) proteins resulting in increased Bax:Bcl-2 ratio in TMZ treated cells. Western blot analyses also detected overexpression of calpain and caspase-3, which cleaved 270 kD α-spectrin at specific sites for generation of 145 and 120 kD spectrin break down products (SBDPs), respectively. However, 1-h pretreatment of cells with 40 μM DXM dramatically decreased TMZ induced apoptosis, decreasing Bax:Bcl-2 ratio and SBDPs. Our results revealed an antagonistic effect of DXM on TMZ induced apoptosis in human glioblastoma U87MG cells, implying that treatment of glioblastoma patients with DXM prior to chemotherapy with TMZ might result in an undesirable clinical outcome.
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DOI：
10.2174/1566524013364239
发表时间：
2001-03-01
期刊：
Current Molecular Medicine (Hilversum)
影响因子：
--
作者：
Olson, M.;Kornbluth, S.
通讯作者：
Kornbluth, S.
影响因子：
45.3
作者：
Osoba, D;Brada, M;Prados, M
通讯作者：
Prados, M
影响因子：
9.2
作者：
Jacobson, MD
通讯作者：
Jacobson, MD
DOI：
10.1016/0960-0760(95)00034-w
发表时间：
1995-06-01
影响因子：
4.1
作者：
EVANSSTORMS, RB;CIDLOWSKI, JA
通讯作者：
CIDLOWSKI, JA
影响因子：
4.1
作者：
Nath, R;Raser, KJ;Wang, KKW
通讯作者：
Wang, KKW