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Water as a tumoricidal agent in bladder cancer. In vitro studies in parental and resistant cell lines
L Z Solomon1, B R Birch, A J Cooper
1Department of Urology, Southampton University Hospitals NHS Trust, Southampton, UK.
Objective:
Water is widely used as a tumoricidal agent during transurethral resection of bladder tumour (TURBT). Despite this, recurrences are common. One possible explanation may be that while the parental bladder cancer cells are sensitive to water, their multidrug resistant (MDR) clones which occur commonly, may be resistant to it. If so, is this a preserve of the MDR phenotype or do other mechanisms confer resistance to water?
Methods:
The parental human urothelial cancer cell lines (MGHU-1 and RT112) and their drug-resistant variants (MDR and non-MDR) were exposed to short pulses of water. The MDR status of these cells was verified using confocal microscopy to detect intracellular accumulation of fluorescent drug (epirubicin). A clonogenic assay was used to establish tumoricidal efficacy on cells in suspension. A thiozolyl blue (MTT) assay was used on adherent cells to assess the residual viable biomass.
Results:
In the MDR clone of cells, colony counts were reduced by 20% after treatment with water as compared to a 60% reduction in the parental cell line. There was a similar reduction in colony counts between the parental RT112 and its non-MDR cisplatin resistant variant.
Conclusion:
Water is less effective on MDR cells. Resistance to water may be a function of the MDR phenotype.
Insights
Water is less effective against multidrug-resistant (MDR) bladder cancer cells. This suggests MDR phenotypes may confer resistance to water, impacting transurethral resection of bladder tumor (TURBT) outcomes.
Area of Science:
- Oncology
- Cell Biology
- Cancer Therapeutics
Background:
- Transurethral resection of bladder tumor (TURBT) commonly uses water as a tumoricidal agent.
- Recurrent bladder tumors after TURBT suggest potential resistance mechanisms.
- Multidrug resistance (MDR) is a known phenomenon in cancer, potentially affecting treatment efficacy.
Purpose of the Study:
- To investigate the efficacy of water as a tumoricidal agent on multidrug-resistant (MDR) bladder cancer cells.
- To determine if the MDR phenotype confers resistance to water treatment.
- To explore alternative resistance mechanisms beyond MDR.
Main Methods:
- Human urothelial cancer cell lines (parental and drug-resistant variants) were utilized.
- Cells were exposed to short water pulses, and MDR status was confirmed via epirubicin accumulation assays.
- Colony formation and MTT assays assessed tumoricidal efficacy and residual viable biomass.
Main Results:
- MDR bladder cancer cell clones showed a 20% reduction in colony counts post-water treatment, compared to 60% in parental cells.
- A similar reduction in efficacy was observed between parental cells and their non-MDR cisplatin-resistant variants.
- These findings indicate reduced sensitivity of MDR cells to water.
Conclusions:
- Water demonstrates reduced tumoricidal effectiveness against multidrug-resistant (MDR) bladder cancer cells.
- The MDR phenotype appears to be a significant factor in conferring resistance to water.
- This resistance may contribute to tumor recurrence after TURBT.