Characterization of molecular events in a series of bladder urothelial carcinoma cell lines with progressive resistance to arsenic trioxide.

Abstract:

:Our previous studies have shown that arsenic trioxide (As2O3), a novel anti-cancer agent, may be active against urothelial carcinomas. A series of bladder urothelial carcinoma cells with progressive As2O3 resistance were established and studied to reveal molecular events in relation to the mechanisms of resistance to As2O3. A sensitive parental line (NTUB1) and three As2O3-resistant sublines (NTUB1/As) were used with their IC50s being 0.9, 1.2, 2.5 and 4.9 microM, respectively. Cellular resistance to As2O3 was associated with a lowered proliferation profile (increased p53 and p21Waf1/Cip1 and decreased c-Myc levels) and a greater resistance to apoptosis (elevated Bcl-2 levels). Cells with a stronger resistance had higher expressions of superoxide dismutase (Cu/Zn) and hMSH2 (but not hMLH1). GSH contents were up-regulated in resistant cells in a dose-dependent manner. The DNA-binding activities of NF-kappaB and AP-1 were down-regulated in resistant cells in a dose-dependent manner. Profound molecular alterations occur during the acquisition of secondary As2O3 resistance. Our in vitro cellular model may help to reveal resistance mechanisms to As2O3 in bladder urothelial carcinoma cells.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Hour TC,Huang CY,Lin CC,Chen J,Guan JY,Lee JM,Pu YS

doi

10.1097/00001813-200409000-00007

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

779-85

issue

8

eissn

0959-4973

issn

1473-5741

pii

00001813-200409000-00007

journal_volume

15

pub_type

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