Mechanism of cisplatin resistance in human urothelial carcinoma cells.
An isogenic pair of cisplatin-susceptible (NTUB1) and -resistant (NTUB1/P) human urothelial carcinoma cell lines was used to elucidate the mechanism of cisplatin resistance. The significantly lower intracellular platinum (IP) concentration, which resulted from the decreased cisplatin uptake, was found in NTUB1/P cells. The enhancement of IP concentration did not increase the susceptibility of NTUB1/P cells to cisplatin treatment. The reduction of IP concentration as well was unable to enhance the cisplatin-resistance in susceptible NTUB1 cells. This indicated that reduction of IP concentration was not the account for the development of cisplatin resistance here. Instead, the over expression of anti-apoptotic Bcl-2, anti-oxidative heme oxygenase-1 (HO-1) and cell cycle regulator p16INK4 seemed to be more important for the gaining of cisplatin in these human urothelial carcinoma cell.
Graduate Institute of Life Sciences, National Defense Medical Center, 161Minquan E. Road, Section 6, Neihu Dist., Taipei City 114, Taiwan, ROC. yhm@gate.sinica.edu.tw,
Hui-Min
HM
Yu
Tsing-Cheng
TC
Wang
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D001483:Base Sequence; D002945:Cisplatin / Q000494:pharmacology*; D017931:DNA Primers; D019008:Drug Resistance, Neoplasm; D006801:Humans; D034741:RNA, Small Interfering; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D017931:DNA Primers; D034741:RNA, Small Interfering; D002945:Cisplatin