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Suberoylanilide Hydroxamic Acid Can Re-sensitize a Cisplatin-Resistant Human Bladder Cancer
Hoyoung Ryu1, Hyunjin Jin1, Jin-Nyoung Ho1
1Department of Urology, Seoul National University Bundang Hospital.
Biological & Pharmaceutical Bulletin
|January 5, 2019
Summary
Suberoylanilide hydroxamic acid (SAHA) shows a synergistic effect with cisplatin in cisplatin-resistant bladder cancer cells. This combination therapy re-sensitizes cancer cells by inducing apoptosis and cell cycle arrest, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Pharmacology
Background:
- Cisplatin is a standard chemotherapy for metastatic urothelial carcinoma.
- Limited survival necessitates novel treatments for cisplatin-resistant bladder cancer.
- Targeting programmed death-ligand 1 (PD-L1) offers second-line options, but more effective therapies are needed.
Purpose of the Study:
- To investigate the synergistic anti-cancer effect of cisplatin combined with suberoylanilide hydroxamic acid (SAHA) in cisplatin-resistant bladder cancer cells.
- To evaluate the impact of this combination on tumor cell proliferation, cell cycle, and apoptosis.
Main Methods:
- Cell counting kit (CCK)-8 assays for proliferation.
- Flow cytometry for cell cycle analysis.
- Western blot for apoptosis-related protein expression (caspase, Bcl-2, BAD).
- Combination index (CI) to assess synergistic effects.
Main Results:
- SAHA and cisplatin demonstrated a strong synergistic anti-cancer effect in cisplatin-resistant bladder cancer cells (T24R2).
- The combination induced cell cycle arrest and apoptosis.
- Western blot revealed caspase activation, decreased anti-apoptotic Bcl-2, and increased pro-apoptotic BAD expression.
- SAHA partially re-sensitized T24R2 cells to cisplatin.
Conclusions:
- SAHA synergistically enhances the anti-cancer activity of cisplatin in resistant bladder cancer cells.
- The combination therapy works by inducing apoptosis and cell cycle arrest.
- SAHA-based treatment represents a potential therapeutic strategy for cisplatin-resistant bladder cancer.
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