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Insulin-like growth factor-I decreased etoposide-induced apoptosis in glioma cells by increasing bcl-2 expression and decreasing CPP32 activity.
- Source :
- Neurological Research; Jan2005, Vol. 27 Issue 1, p27-35, 9p, 6 Diagrams, 3 Graphs
- Publication Year :
- 2005
-
Abstract
- Aims: In a variety of tumors, the susceptibility of the tumor cells to apoptotic cell death following chemotherapy is a major determinant of therapeutic outcome. Gliomas are resistant to most chemotherapeutic agents, and its mechanism is not known in detail. In an attempt to understand the mechanism of chemo-resistance, we investigated the roles of insulin-like growth factor-I (IGF-I), IGF-I receptors (IGF-IR), and their relationship with the apoptotic response of two glioma cell lines to etoposide, a chemotherapeutic agent for malignant gliomas. Methods: Two human glioma cell lines, U-87MG and KNS-42, were used. Etoposide-induced cell growth inhibition was quantified using a modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide), colorimetric assay. Hoechst 33258 staining, DNA fragmentation assay, and western blot were used for the evaluation of apoptosis. ApoAlert<superscript>TM</superscript> caspase assay was used for measuring the activity of caspase-3 (CPP32) and interleukin-1 β -converting enzyme (ICE) protease. In addition, the effect of IGF-IR antisense was tested in U-87MG and KNS-42 glioma cell lines. Results: Etoposide inhibited the growth of U-87MG and KNS-42 cells in a concentrationdependent manner. Etoposide increased the expression of wild-type p53, activated CPP32 (but not ICE) activity, and induced apoptosis in these cells. IGF-I prevented etoposide-induced apoptosis by increasing the expression of bcl-2 and decreasing the activity of CPP32. IGF-IR antisense enhanced the apoptotic effect of etoposide. Conclusions IGF-I decreased etoposideinduced apoptosis in glioma cells by increasing the expression of bcl-2 and decreasing the activity of CPP32. The antisense of IGF-IR increased etoposide-induced apoptosis. The antiapoptotic effect of IGF-I and IGF-IR might be related to the chemo-resistance of glioma to chemotherapeutic agents. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01616412
- Volume :
- 27
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Neurological Research
- Publication Type :
- Academic Journal
- Accession number :
- 19968542
- Full Text :
- https://doi.org/10.1179/016164105X18151