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Published on: January 22, 2013
Expression of resistance-related proteins in nephroblastoma after chemotherapy
M Volm1, J Mattern, G Stammler
1German Cancer Research Center, Heidelberg, Germany.
Abstract:
Tumor tissues of untreated and cytostatic-agent-treated patients with nephroblastomas were investigated for expression of resistance-related proteins (P-glycoprotein, glutathione S-transferase-pi, glutathione peroxidase and topoisomerase II) to ascertain whether resistance proteins are changed after treatment. Tumor tissue was analyzed by means of mRNA. Twenty-three children were treated with actinomycin D and vincristine for 4 to 8 weeks. Eight children received no preoperative chemotherapy. In untreated patients, no expression of P-glycoprotein was seen, whereas, in the patients who were treated with actinomycin D and vincristine, 12 out of 23 tumors showed increased P-glycoprotein expression (> mean value). Although we found no difference between treated and untreated tumors for glutathione S-transferase-pi, we found significant differences in the expression of glutathione peroxidase. In the 8 untreated patients, 7 tumors showed low glutathione peroxidase (< mean value) and one high (> mean value) glutathione-peroxidase-mRNA content. With treatment, 11 tumors expressed low levels and 12 tumors high levels of mRNA. A significant positive correlation between P-glycoprotein and glutathione peroxidase was found. In addition, of the 8 untreated patients, 2 had low topoisomerase-II expression, and 6 high expression. With treatment, the expression was reduced in 18 tumors, and only 5 tumors had high levels of this protein. These results were confirmed by PCR and immunohistochemistry.
Insights
Cytostatic treatment for nephroblastoma increased P-glycoprotein and altered glutathione peroxidase expression. Topoisomerase II levels decreased after treatment, suggesting chemotherapy impacts resistance proteins.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Nephroblastoma treatment response can be influenced by drug resistance proteins.
- Understanding changes in these proteins after chemotherapy is crucial for treatment optimization.
Purpose of the Study:
- To investigate the expression of key resistance-related proteins in nephroblastoma tumors before and after cytostatic treatment.
- To determine if actinomycin D and vincristine therapy alters the expression of P-glycoprotein, glutathione S-transferase-pi, glutathione peroxidase, and topoisomerase II.
Main Methods:
- Analysis of tumor tissue mRNA from 31 nephroblastoma patients (23 treated, 8 untreated).
- Quantitative assessment of P-glycoprotein, glutathione S-transferase-pi, glutathione peroxidase, and topoisomerase II expression.
- Confirmation of results using Polymerase Chain Reaction (PCR) and immunohistochemistry.
Main Results:
- P-glycoprotein expression was absent in untreated tumors but increased in 12/23 treated tumors.
- Glutathione peroxidase mRNA levels showed significant differences between treated and untreated groups.
- Topoisomerase II expression was reduced in 18/23 treated tumors compared to untreated ones.
- A significant positive correlation was observed between P-glycoprotein and glutathione peroxidase expression.
Conclusions:
- Cytostatic chemotherapy with actinomycin D and vincristine significantly alters the expression of P-glycoprotein, glutathione peroxidase, and topoisomerase II in nephroblastoma.
- These changes suggest a role for these proteins in mediating treatment response or resistance.
- Further research is warranted to explore the clinical implications of these altered protein expressions.
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