抑制多胺调节因子-1表达增强地塞米松对人宫颈癌细胞的抗肿瘤活性  

Inhibiting expression of polyamines regulator-1 can enhance the antitumor activity of dexamethasone on human cervical cancer cells

作　　者：杨建林[1] 李论[1] 曾子悦 曹春雨[1] 吕亚丰 秦宇[1] 王艳林[1] YANG Jianlin;LI Lun;ZENG Ziyue;CAO Chunyu;LYU Yafeng;QIN Yu;WANG Yanlin(Key Laboratory of Tumor Microenviron- ment and Immunotherapy of Hubei Province,Medical College of Three Gorges University,Yichang 443002,Hubei,Chin)

机构地区：[1]三峡大学医学院肿瘤微环境与免疫治疗湖北省重点实验室,湖北宜昌443002

出　　处：《中国肿瘤生物治疗杂志》2018年第7期711-715,共5页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No.81372265);湖北省高等学校优秀中青年创新团队计划项目(No.T201203);肿瘤微环境与免疫治疗湖北省重点实验室(三峡大学)开放基金(No.2016KZL04)~~

摘　　要：目的:探讨在人宫颈癌Caski细胞中抑制多胺调节因子-1(polyamine-modulated factor,PMF-1)表达对糖皮质激素类药物地塞米松(dexamethasone,DEX)抗肿瘤作用的影响。方法:设计合成靶向人PMF-1基因的si RNA,Western blotting法鉴定其对Caski细胞PMF-1中表达的影响。用DEX处理PMF-1表达抑制的Caski细胞和对照细胞,然后分析PMF-1表达下调是否影响瘤细胞对DEX的敏感性。MTT法检测细胞增殖,流式细胞术分析细胞周期,Western blotting法测定糖皮质激素受体(glucocorticoids receptor,GR)的表达水平,高效液相色谱法分析细胞内的多胺含量。结果:用靶向PMF-1基因的siRNA瞬时转染Caski细胞能显著性下调细胞中PMF-1蛋白的表达水平。与对照细胞相比,用DEX处理PMF-1表达下调的Caski细胞能更有效地抑制细胞增殖(P<0.01),上调细胞内GR表达水平(P<0.01),并显著抑制细胞分裂导致G2周期阻滞(P<0.01),同时能显著性地降低细胞内的多胺水平(P<0.01)。结论:抑制PMF-1表达可增强DEX对人宫颈癌细胞的抗肿瘤活性,其机制可能与降低细胞内多胺水平和增强细胞周期阻滞相关。Objective： To investigate the influence of inhibiting expression of polyamine-modulated factor （PMF-1） on the antitumor effect of glucocorticoid dexamethasone （DEX） in human cervical cancer Caski cells. Methods： siRNAs which target human PMF-1 gene were designed and synthesized, and their effect on the expression of PMF-1 in Caski cells was evaluated by Western blotting. The PMF-1 down-regulated and control Caski cells were treated with DEX, and then the affect of PMF-1 down regulation on the sensitivity of the tumor cells to DEX was analyzed. MTT method was used to detect cell proliferation, flow cytometry was used to analyze cell cycle,Western blotting method was used to evaluate expression level of glucocorticoids receptor （GR）, and HPLC was used to analyze intracellular polyamine content. Results： The transient transfection of Caski cells with siRNA which targets PMF-1 gene can significantly reduce the expression level of PMF-1 protein. Compared with the control cells, treating PMF-1 down-regulated Caski cells with DEX can more effectively inhibit cell proliferation（P〈0.01）, up regulate GR expression, arrest cell cycle at G2 stage（P〈0.01）, and also significantly reduce intracellular polyamine level（P〈0.01）. Conclusion：Inhibiting PMF-1 expression can enhance antitumor pharmacological activity of DEX against human cervical cancer cells, and the underlying mechanism may be related with enhanced cell cycle inhibition and decreased intracellular polyamine level.

关 键 词：多胺调节因子-1 宫颈癌细胞 CASKI细胞 地塞米松 药物敏感性 

分 类 号：R737.3[医药卫生—肿瘤] R730.54[医药卫生—临床医学]