Tamoxifen modulation of carboplatin cytotoxicity in a human U-138 glioma cell line
Tamoxifen modulation of carboplatin cytotoxicity in a human U-138 glioma cell line
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DOI：
10.1016/s0303-8467(98)00004-3
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发表时间：
1998-06-01
影响因子：
1.9
通讯作者：
Ruggeri, A
中科院分区：
文献类型：
--
作者：
Mastronardi, L;Farah, JO;Ruggeri, A
Glioma cells express high protein kinase C (PKC) activity, which may represent an important therapeutic target. Tamoxifen (TAM) has moderate PKC-inhibiting activity, blocking DNA synthesis and cellular proliferation in human glioma cells at concentrations that can be achieved therapeutically. Carboplatin (CBDCA), a second-generation platinum derivative, induces intra- and interstrand DNA-protein crosslinks producing inhibition of tumor-cell growth. In the present study, the effect of TAM. CBDCA, and the combination of both was evaluated against the human established U-138 glioma cell line during the exponential growth phase (48-72 h) by means of both the Biorad protein assay (BPA) method and Trypan blue exclusion study (TBES). Both TAM and CBDCA reduced the cellular growth rate, with a median 50%-inhibiting concentration (IC50) of 12.5 mu M for TAM and 350 mu M for CBDCA. The U-138 glioma cell line showed a moderate response to 100 mu M Of CBDCA, with less than or equal to 10% reduction of the growth rate. The association of both chemotherapeutic agents induced a 98% reduction of the IC50 dose of TAM (0.1 mu M), and a 71% reduction of the IC50 dose of CBDCA (100 mu M). During the combinational TAM-CBDCA exposure we observed a cytotoxic effect of TAM at concentrations lower than 0.1 mu M, not recognized using it as a single drug. The differences observed among the IC50 doses (TAM, CBDCA, TAM-CBDCA) and among treated and untreated matched control cells were statistically significant (P < 0.01). Our results confirm previous observations about the efficacy in vitro of TAM against human glioma cell lines and show a marked enhancement of this activity by CBDCA. (C) 1998 Elsevier Science B.V. All rights reserved.
