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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。
Objective: To study the effect of retinoic acid and interferon on the growth inhibition and apoptosis induction of bladder cancer cells and its possible molecular mechanism. METHODS: Four groups of bladder cancer cells were treated with all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9cRA) combined with interferon α 2a (IFNα 2a). TUNEL, FCM, To observe the effect of retinoic acid and interferon alone or in combination on the growth inhibition and apoptosis induction of different bladder cancer cell lines and the changes of nuclear retinoic acid receptor and STAT1 protein. Results: ATRA and 9cRA had no significant effect on the growth inhibition and apoptosis induction of all bladder cancer cells, while IFNα 2a enhanced the effect of ATRA and 9cRA on bladder cancer. Combined use of ATRA and IFNα 2a induced bladder cancer cells RARβ and Stat1 expression. CONCLUSION: IFNα 2a can synergize with ATRA and 9cRA on bladder cancer cell growth inhibition and apoptosis-inducing effect. Up-regulation of STAT1 gene expression may be its main molecular mechanism. The experiment shows that synergistic effect of retinoic acid and interferon in the treatment of bladder transitional cell carcinoma .