褪黑素增强紫杉醇对膀胱癌T24细胞增殖的抑制作用  

Melatonin enhances the inhibitory effect of paclitaxel on T24 cell proliferation

作　　者：陈欢 朱佳斌 赵晓瑾 董传江[1] 董自强[1] CHEN Huan;ZHU Jia-bin;ZHAO Xiao-jin;DONG Chuan-jiang;DONG Zi-qiang(Department of Urology,the First College of Clinical Medical Science of Three Gorges University,Yichang 443000,China;Department of Neurosurgery,the Affiliated Renhe Hospital of China Three Gorges University)

机构地区：[1]三峡大学第一临床医学院泌尿外科,湖北省宜昌市443000 [2]三峡大学附属仁和医院神经外科

出　　处：《天津医药》2020年第5期353-357,I0001,共6页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(81300626)。

摘　　要：目的观察褪黑素(melatonin,Mel)与紫杉醇(paclitaxel,PTX)协同对膀胱癌T24细胞的抑制作用,并探讨其作用机制。方法Mel和化疗药物PTX单独使用或者联合使用处理T24细胞,用CCK-8法和平板克隆形成实验检测Mel和PTX对T24细胞的增殖抑制作用及半数抑制浓度(IC50);RT-PCR和Western-blot检测T24细胞中环氧化物酶-2(COX-2)的mRNA和蛋白水平;采用双荧光素酶报告基因检测NF-kB的启动子区活性。结果与单独PTX组相比,Mel能够显著增强PTX对T24细胞增殖的抑制作用并降低PTX的IC50值,T24细胞的增殖能力、克隆形成能力显著下降(P<0.05);联合用药可以显著降低COX-2的mRNA和蛋白水平及其相关信号通路核转录因子(NF)-kB的启动子活性。结论Mel与PTX可协同抑制T24膀胱癌细胞的增殖,其机制可能与抑制NF-kB信号通路启动子活性,从而降低T24细胞内COX-2的表达有关。ObjectiveTo observe the inhibitory effect of melatonin(Mel)and paclitaxel(PTX)on T24 bladder cancercells and to explore the underlying mechanism.MethodsT24 cells were treated with Mel and PTX alone or incombination.CCK-8 assay and plate colony formation assay were used to detect the proliferation inhibition or IC50 value ofMel and PTX on T24 cells.The m RNA and protein levels of COX-2 in T24 cells were detected by RT-PCR and Westernblot assays.The promoter activity of NF-kB was detected by dual-luciferase reporter assay.ResultsCompared with thePTX treatment alone,Mel can significantly enhance the inhibitory effect of PTX on T24 cell proliferation and decrease theIC50 value of PTX.The proliferation and colony formation ability of T24 cells were decreased significantly(P<0.05).Combination therapy with Mel and PTX could significantly reduce the protein and m RNA level of COX-2 and the promoteractivity of its related NF-kB signaling pathway.ConclusionMel and PTX could synergistically inhibit the proliferation ofT24 bladder cancer cells,which may be related to the inhibition of NF-kB signaling pathway promoter activity and thedecrease of COX-2 expression in T24 cells.

关 键 词：褪黑激素 紫杉酚 膀胱肿瘤 环氧化酶2 NF-κB 

分 类 号：R737.14[医药卫生—肿瘤]