Growth Inhibition and Apoptosis Induced by Retinoic Acid Combined with Interferon Alpha-2a on Transitional Cell Carcinoma of Bladder

摘要

Objective: To identify new favorable agents and develop novel approaches for the chemoprevention and treatment of superficial bladder cancer and investigate the effects of combination of retinoids and interferon α-2a on growth inhibition and apoptosis induction in bladder cancer cell lines. Methods: Tour bladder cancer cell lines, grade 1 to 3, and two retinoids, all-trans-retinoic acid(ATRA) , 9-cis retinoiC acid(9cRA), combined with interferon α-2a(INF), were used in the study. We compared the competence of these agents to inhibit growth, induce apoptosis, affect the expression of nuclear retinoid receptors, and modulate STAT1 protein. Results: Most of the bladder cancer cell lines were resistant to the effect of ATRA and 9cRA on growth inhibition and apoptosis induction, even at higher concentra tion(10~(-5)M). The effects of ATRA and 9c RA on cell growth and apoptosis were enhanced by INFα-2a.Combination of ATRA and IFNα-2a induced RARβ and Stat 1 expression in three bladder cancer cell lines. Conclusion: The results demonstrated that INFα-2a synergize with the inhibitory effect of ATRA and 9c RA on the growth inhibition and apoptosis of bladder cancer cells in vitro, which suggested that it has a potential interest for the treatment of transitional cell carcinoma of bladder.