Cisplatin (CDDP)-induced radiation resistance is not associated with CDDP resistance in 86HG39 and A172 malignant glioma cells.
Malignant gliomas are often treated with cisplatin (cis-diamminedichloroplatinum(II), CDDP) and radiation but results remain unsatisfactory. The development of resistance might explain the poor prognosis. The aim of this study was to investigate whether two human malignant glioma cell lines, 86HG39 and A172, develop resistance to CDDP and/or radiation after CDDP pretreatment. The cells are incubated three times with 10(-6) M CDDP for 24 h, allowed to recover from the treatment and then tested for sensitivity to CDDP and radiation (9 Gy, 60Co) using a colorimetric assay (MTT). A172 pretreated and wild-type cells showed no difference in sensitivity to CDDP, whilst 86HG39 cells became more sensitive following pretreatment. This indicates that no resistant phenotype towards CDDP developed in any of the cell lines. In contrast, the CDDP-pretreated cells, after radiation, had significantly higher growth rates compared with the wild-type cells in both cell lines (A172: 4.4 +/- 0.5 versus 2.5 +/- 0.3, respectively, 192 h after radiation; 86HG39: 6.2 +/- 0.7 versus 2.3 +/- 0.3, respectively, 216 h after radiation; P < 0.05) indicating resistance against radiation. The level of glutathione (GSH), which is known to mediate resistance against radiation, was 157.2 +/- 61.3 ng/mg protein in A172 cells and 93.2 +/- 16.9 ng/mg protein in 86HG39 cells, and there was no significant difference between levels in wild-type and pretreated cells (A172: 130.1 +/- 34; 86HG39: 81.6 +/- 10.4). These data show that CDDP pretreatment can induce resistance against radiation in vitro independently of CDDP cross-resistance mediated by a mechanism different from GSH.
Poppenborg
H
H
Department of Clinical Pharmacology, University of Leipzig, Germany. popph@medizin.uni-leipzig.de
Knüpfer
M M
MM
Preiss
R
R
Wolff
J E
JE
Galla
H J
HJ
D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D011838:Radiation-Sensitizing Agents; D002945:Cisplatin