维甲酸和干扰素联合应用诱导膀胱癌细胞凋亡的实验研究

目的 :研究维甲酸和干扰素联合应用对膀胱癌细胞的生长抑制和诱导凋亡的作用及其可能分子机制。方法 :应用全反式维甲酸 (ATRA)和 9-顺式维甲酸 (9cRA)联合干扰素α 2a(IFNα 2a)作用于 4组膀胱癌细胞 ,运用TUN NEL、FCM、RT PCR及Western等技术观察维甲酸、干扰素单独或联合应用对不同膀胱癌细胞株的生长抑制、诱导凋亡的影响以及核维甲酸类受体、STAT1蛋白等方面的改变。结果 :ATRA和 9cRA对所有膀胱癌细胞的抑制生长和诱导凋亡作用均不明显 ,而IFNα 2a能增强ATRA和 9cRA对膀胱癌的这种作用 ,且联合应用ATRA和IFNα 2a能诱导膀胱癌细胞RARβ和Stat1的表达。结论 :IFNα 2a能协同ATRA和9cRA对膀胱癌细胞生长抑制和凋亡诱导效应 ,上调STAT1基因表达可能是其主要分子机制 ,实验显示了维甲酸和干扰素联合应用治疗膀胱移行细胞癌的协同作用。

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

Objective: To identify new favorable agents and develop novel approaches for the chemoprevention and treatnent 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: Four 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 apeptosis, 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 concentration(10- 5M). The effects of ATRA and 9c RA on cell growth and apoptosis were enhanced by INF α-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.