title: Hydrostatic pressure enhances mitomycin C induced apoptosis in urothelial carcinoma cells.
abstract: OBJECTIVE
  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
  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 10 kPa hydrostatic pressure, MMC treatment induced increasing FasL expression. The mitochondria of UC cells displayed increasingly impaired membrane potentials following a combined treatment with 10 μg/ml MMC and 10 kPa 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.
authors: 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.
authors: Shao-Kuan
authors: SK
authors: Chen
authors: Department of Mechanical Engineering, National Central University, Jhongli, Taiwan; Institute of Biomedical Engineering, National Central University, Jhongli, Taiwan.
authors: Chih-Ang
authors: CA
authors: Chung
authors: Institute of Biomedical Engineering, National Central University, Jhongli, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan.
authors: Yu-Che
authors: YC
authors: Cheng
authors: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors: Chi-Jung
authors: CJ
authors: Huang
authors: Institute of Biomedical Engineering, National Central University, Jhongli, Taiwan; Department of Chemical and Materials Engineering, National Central University, Jhongli, Taiwan.
authors: Ruoh-Chyu
authors: RC
authors: Ruaan
authors: Department of Chemical and Materials Engineering, National Central University, Jhongli, Taiwan.
authors: Wen-Yih
authors: WY
authors: Chen
authors: Department of Mechanical Engineering, National Central University, Jhongli, Taiwan.
authors: Chuan
authors: C
authors: Li
authors: Department of Mechanical Engineering, National Central University, Jhongli, Taiwan.
authors: Chia-Wen
authors: CW
authors: Tsao
authors: Department of Chemical and Materials Engineering, National Central University, Jhongli, Taiwan.
authors: Wei-Wen
authors: WW
authors: Hu
authors: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Institute of Biomedical Engineering, National Central University, Jhongli, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan; Department of Anesthesiology, Sijhih Cathay General Hospital, Sijhih District, New Taipei City, Taiwan. Electronic address: chiencmail@yahoo.com.tw.
authors: Chih-Cheng
authors: CC
authors: Chien
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D017209:Apoptosis; D019149:Bioreactors; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004867:Equipment Design; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D006874:Hydrostatic Pressure; D053078:Membrane Potential, Mitochondrial; D016685:Mitomycin / Q000008:administration & dosage*; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D019459:Urothelium / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016685:Mitomycin; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; BCG; Bacillus Calmette-Guerin; MMC; MTT; RT-PCR; TURBT; UC; mitomycin C; qRT-PCR; quantitation RT-PCR; reverse transcription-PCR; transurethral resection of the bladder tumor; urothelial carcinoma