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Expression of basic fibroblast growth factor is associated with resistance to cisplatin in a human bladder cancer
Abstract:
To clarify the role of basic fibroblast growth factor (FGF-2) in the drug resistance of bladder cancer, we transfected the FGF-2 gene into HT1376, an FGF-2 negative human bladder cancer cell line. The FGF-2-transfected cell lines exhibited three- to four-fold higher resistant potential to cisplatin than the vector-only transfected control cell lines in vitro. When cisplatin was injected intraperitoneally after s.c. implantation of HT1376 sublines into nude mice, FGF-2 transfectants formed tumors about twice as large as did controls. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among these cell lines without cisplatin treatment. Furthermore, DNA degradation following cisplatin treatment was markedly suppressed in FGF-2 transfectants compared to control cells. These results suggest that the expression of the FGF-2 gene plays an important role in the acquisition of the cisplatin-resistant phenotype of bladder cancer, probably through the protection against cisplatin-induced apoptosis.
Insights
Basic fibroblast growth factor (FGF-2) enhances bladder cancer drug resistance. FGF-2 gene expression increases resistance to cisplatin and suppresses apoptosis, suggesting a key role in treatment failure.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer remains a significant health concern with challenges in treatment efficacy.
- Drug resistance, particularly to platinum-based chemotherapeutics like cisplatin, is a major obstacle in managing bladder cancer.
- The role of specific growth factors, such as basic fibroblast growth factor (FGF-2), in mediating this resistance is not fully understood.
Purpose of the Study:
- To investigate the functional role of basic fibroblast growth factor (FGF-2) in the development of cisplatin resistance in human bladder cancer cells.
- To determine if FGF-2 expression influences the response of bladder cancer to cisplatin treatment both in vitro and in vivo.
Main Methods:
- Transfection of the FGF-2 gene into HT1376, an FGF-2-negative human bladder cancer cell line.
- In vitro assessment of cisplatin resistance and cell proliferation in transfected and control cell lines.
- In vivo studies involving subcutaneous implantation of cell lines into nude mice, followed by cisplatin treatment and tumor growth evaluation.
- Analysis of DNA degradation as an indicator of apoptosis following cisplatin exposure.
Main Results:
- FGF-2-transfected bladder cancer cells demonstrated a three- to four-fold increase in resistance to cisplatin in vitro compared to controls.
- Tumors derived from FGF-2 transfectants were approximately twice as large as control tumors when treated with cisplatin in vivo.
- No significant differences in cell proliferation or tumor growth were observed between FGF-2 transfectants and controls in the absence of cisplatin.
- Cisplatin-induced DNA degradation was significantly suppressed in FGF-2-expressing cells, indicating reduced apoptosis.
Conclusions:
- Expression of the FGF-2 gene significantly contributes to the acquisition of cisplatin resistance in bladder cancer.
- FGF-2 likely confers resistance by protecting bladder cancer cells against cisplatin-induced apoptosis.
- Targeting FGF-2 signaling may represent a potential therapeutic strategy to overcome cisplatin resistance in bladder cancer.