La蛋白抑制剂Comp 1120通过53BP1途径增强卵巢癌细胞对卡铂的敏感性  

La protein inhibitor Comp 1120 enhances the sensitivity of ovarian cancer cells to carboplatin via the 53BP1 pathway

作　　者：李俊慜 朱佳蕾 汤静 LI Junmin;ZHU Jialei;TANG Jing(Obstetrics&Gynecology Hospital of Fudan University,Shanghai 200090,China)

机构地区：[1]复旦大学附属妇产科医院,上海200090

出　　处：《中国临床药学杂志》2025年第2期81-86,共6页Chinese Journal of Clinical Pharmacy

基　　金：中华医学会临床药学分会2023年度临床药学科研基金(编号Z-2021-46-2101-2023);上海市青浦区卫生健康系统第五轮学科带头人培养计划(编号XD2023-10)。

摘　　要：目的探讨La蛋白抑制剂Comp 1120在增强卵巢癌细胞对卡铂的敏感性中的作用机制。方法使用A2780卵巢癌细胞株评估Comp 1120与卡铂联合使用的效果,特别关注P53结合蛋白1(53BP1)在此过程中的作用。采用Western blot、TUNEL实验和流式细胞术评估细胞凋亡情况。结果Western blot分析显示,在卡铂与Comp 1120联合处理下,A2780卵巢癌细胞中促凋亡蛋白Caspase-3和BAX的表达显著上调(P<0.01),而抗凋亡蛋白Bcl-2的表达下调(P<0.01)。TUNEL实验和流式细胞术进一步证实,卡铂与Comp 1120联合使用显著促进了细胞凋亡(P<0.01)。所有实验结果均显示,这种促凋亡效应依赖于53BP1的表达;在53BP1基因沉默的细胞中,联合处理的促凋亡效应显著减弱(P<0.01),提示Comp 1120增强卡铂敏感性通过53BP1调控实现。结论La蛋白抑制剂Comp 1120能有效增强卵巢癌细胞对卡铂的敏感性,其作用机制可能涉及对53BP1途径的调节。AIM To explore the role of La protein inhibitor Comp 1120 in enhancing the sensitivity of ovarian cancer cells to carboplatin.METHODS The effect of the combined use of Comp 1120 and carboplatin was evaluated using the A2780 ovarian cancer cell line,with a particular focus on the role of 53BP1 in this process.Cell apoptosis was assessed using Western blot,TUNEL assays,and flow cytometry.RESULTS Western blot analysis showed that in A2780 ovarian cancer cells treated with the combination of carboplatin and Comp 1120,the expressions of pro-apoptotic proteins Caspase-3 and BAX were significantly upregulated(P<0.01),while the expression of the anti-apoptotic protein Bcl-2 was downregulated(P<0.01).TUNEL assay and flow cytometry further confirmed that the combination of carboplatin and Comp 1120 significantly promoted cell apoptosis(P<0.01).All experimental results indicated that this pro-apoptotic effect depended on the expression of 53BP1.The pro-apoptotic effect of the combined treatment was significantly reduced in cells with 53BP1 gene silencing(P<0.01),suggesting that Comp 1120 enhanced carboplatin sensitivity through 53BP1 regulation.CONCLUSION This study demonstrates that the La protein inhibitor Comp 1120 can effectively enhance the sensitivity of ovarian cancer cells to carboplatin,likely involving modulation of the 53BP1 pathway.

关 键 词：LA蛋白 Comp 1120 卵巢癌 卡铂敏感性 53BP1 

分 类 号：R965[医药卫生—药理学]