Hydrostatic pressure enhances mitomycin C induced apoptosis in urothelial carcinoma cells - Abstract

OBJECTIVES: Urothelial carcinoma (UC) of the bladder is the second most common cancer of the genitourinary system.

Clinical UC treatment usually involves transurethral resection of the bladder tumor followed by adjuvant intravesical immunotherapy or chemotherapy to prevent recurrence. Intravesical chemotherapy induces fewer side effects than immunotherapy but is less effective at preventing tumor recurrence. Improvement to intravesical chemotherapy is, therefore, needed.

METHODS AND MATERIALS: Cellular effects of mitomycin C (MMC) and hydrostatic pressure on UC BFTC905 cells were assessed. The viability of the UC cells was determined using cellular proliferation assay. Changes in apoptotic function were evaluated by caspase 3/7 activities, expression of FasL, and loss of mitochondrial membrane potential.

RESULTS: Reduced cell viability was associated with increasing hydrostatic pressure. Caspase 3/7 activities were increased following treatment of the UC cells with MMC or hydrostatic pressure. In combination with 10kPa hydrostatic pressure, MMC treatment induced increasing FasL expression. The mitochondria of UC cells displayed increasingly impaired membrane potentials following a combined treatment with 10μg/ml MMC and 10kPa hydrostatic pressure.

CONCLUSIONS: Both MMC and hydrostatic pressure can induce apoptosis in UC cells through an extrinsic pathway. Hydrostatic pressure specifically increases MMC-induced apoptosis and might minimize the side effects of the chemotherapy by reducing the concentration of the chemical agent. This study provides a new and alternative approach for treatment of patients with UC following transurethral resection of the bladder tumor.

Written by:
Chen SK, Chung CA, Cheng YC, Huang CJ, Ruaan RC, Chen WY, Li C, Tsao CW, Hu WW, Chien CC.   Are you the author?
Department of Urology, Sijhih Cathay General Hospital, New Taipei City, Taiwan; Department of Mechanical Engineering, National Central University, Jhongli, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.

Reference: Urol Oncol. 2013 Feb 8. pii: S1078-1439(12)00336-5.
doi: 10.1016/j.urolonc.2012.09.004


PubMed Abstract
PMID: 23403205

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