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C6 cells cross-resistant to cisplatin and radiation
H Poppenborg1, G Münstermann, M M Knüpfer
1University Hospital of Münster, Department of Pediatric Hematology and Oncology, Germany.
Anticancer Research
|May 1, 1997
Summary
Cisplatin (CDDP) treatment can induce resistance to chemotherapy and radiation in malignant glioma cells. This resistance is linked to increased glutathione levels and potentially genetic mutations.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Malignant gliomas exhibit inherent resistance to standard treatments like radiation and chemotherapy.
- Understanding mechanisms of acquired resistance is crucial for improving therapeutic outcomes.
Purpose of the Study:
- To investigate if cisplatin (cis-diamminedichloroplatinum(II), CDDP) pretreatment induces resistance to CDDP and radiation in C6 glioma cells.
- To explore the potential role of glutathione levels and genetic mutation in CDDP-induced resistance.
Main Methods:
- C6 glioma cells were pretreated with CDDP (10(-6) M for 24 hours).
- Cellular sensitivity to CDDP and radiation (9 Gy 60Co) was assessed using a colorimetric assay.
- Glutathione (GSH) levels were measured.
- Wild-type subclones with varying CDDP sensitivities were established to investigate mutation involvement.
Main Results:
- CDDP-pretreated cells showed a 2.0-fold resistance to CDDP and significantly reduced radiation sensitivity (36.4% vs. 28.6% survival, p=0.005).
- Pretreated cells exhibited higher glutathione levels (51.7 ng/mg protein) compared to control cells (40.4 ng/mg protein, p=0.029).
- Genetic mutation in a subclone led to cross-resistance to both CDDP and radiation, indicating a role for mutation in acquired resistance.
Conclusions:
- CDDP can induce resistance to itself and radiation in glioma cells.
- Elevated glutathione levels and induced genetic mutations are potential mechanisms underlying CDDP-induced chemoresistance and radioresistance.