Growth inhibition and apoptosis induction by retinoic acid and interferon combined use on transitional cell carcinoma of bladder / 中华泌尿外科杂志

ABSTRACT

Objective To investigate the effects of combination of retinoids and interferon ?-2a on growth inhibition and apoptosis induction in bladder cancer cell lines. Methods Four bladder cancer cell lines and two retinoids,all-trans-retinoic acid (ATRA),9-cis retinoic acid (9cRA),combined with interferon ?-2a(IFN),were used in the study.The abilities of these agents to inhibit growth,induce apoptosis were compared and the expression of nuclear retinoid receptors,Stat1 protein were measured by means of TUNEL,FCM,RT-PCR and Western blot. Results Most of the bladder cancer cell lines were resistant to the effect of ATRA and 9cRA on growth inhibition and apoptosis induction.The effects of ATRA and 9cRA on cell growth and apoptosis were enhanced by IFN ?-2a.Combination of ATRA and IFN ?-2a induced RAR? and Stat 1 expression in three bladder cancer cell lines. Conclusions INF ?-2a synergizes with the inhibitory effect of ATRA and 9cRA on the growth inhibition and apoptosis of bladder cancer cells in vitro,up-regutation of Stat1 gene expression could be the main molecular mechanism.