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Intracellular Refolding Assay
Published on: January 24, 2012
Small interfering RNA targeting heat shock protein 70 enhances chemosensitivity in human bladder cancer cells
Hosny M Behnsawy1, Hideaki Miyake, Yuji Kusuda
1Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
Objectives:
To evaluate the expression levels of heat shock protein 70 (HSP70) in human urothelial cancer of the bladder and to assess the therapeutic effects of treatment with small interfering RNA (siRNA) targeting HSP70 on human bladder cancer KoTCC-1 cells.
Materials And Methods:
HSP70 expression in bladder cancer specimens obtained from 235 patients were evaluated by immunohistochemical staining. We then analyzed changes in the growth and chemosensitivity of KoTCC-1 cells following treatment with HSP70 siRNA.
Results:
Expression levels of HSP70 protein in bladder cancer specimens were significantly related to major prognostic indicators, including pathologic stage and tumor grade. Treatment of KoTCC-1 with HSP70 siRNA resulted in a dose-dependent inhibition of HSP70 expression. HSP70 siRNA significantly inhibited the growth of KoTCC-1 compared with that after treatment with scrambled control siRNA. Among several chemotherapeutic agents, the most powerful synergistic cytotoxic effect was observed when KoTCC-1 was treated with gemcitabine plus HSP70 siRNA, which induced more than 50% reduction in the IC50 of gemcitabine. Furthermore, a significant increase in the subG0-G1 fraction of KoTCC-1 and the DNA fragmentation was observed only after combined treatment with HSP70 siRNA and sublethal doses of gemcitabine, but not after treatment with either agent alone. Similarly, caspase-3 and caspase-9, but not caspase-8, in KoTCC-1 were synergistically activated by combined treatment with gemcitabine and HSP70 siRNA.
Conclusions:
Silencing of HSP70 expression using siRNA could be an attractive therapeutic strategy for bladder cancer by inducing inhibition of tumor growth as well as enhancing chemosensitivity.
Insights
Targeting heat shock protein 70 (HSP70) with small interfering RNA (siRNA) inhibits bladder cancer cell growth. Combining HSP70 siRNA with gemcitabine enhances chemotherapy effectiveness and induces cancer cell death.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Heat shock protein 70 (HSP70) is implicated in various cancers, including urothelial carcinoma of the bladder.
- Understanding HSP70's role is crucial for developing novel bladder cancer treatment strategies.
Purpose of the Study:
- To quantify HSP70 expression in human bladder cancer tissues.
- To investigate the therapeutic potential of HSP70-targeting small interfering RNA (siRNA) in human bladder cancer cells (KoTCC-1).
Main Methods:
- Immunohistochemical staining was used to assess HSP70 expression in 235 bladder cancer specimens.
- KoTCC-1 cells were treated with HSP70 siRNA to evaluate effects on cell growth and chemosensitivity.
Main Results:
- HSP70 expression correlated significantly with bladder cancer prognostic factors like pathologic stage and tumor grade.
- HSP70 siRNA treatment dose-dependently reduced HSP70 expression and inhibited KoTCC-1 cell proliferation.
- Combined treatment with HSP70 siRNA and gemcitabine demonstrated synergistic cytotoxicity, significantly reducing gemcitabine's IC50 and inducing DNA fragmentation and apoptosis via caspase-3 and caspase-9 activation.
Conclusions:
- Silencing HSP70 expression via siRNA presents a promising therapeutic approach for bladder cancer.
- This strategy effectively inhibits tumor growth and enhances the sensitivity of cancer cells to chemotherapy.
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