齐慧,呼群,苏乌云,贾永峰,陈连香,曹冉华,乌日罕.EZH2蛋白在非小细胞肺癌顺铂耐药中的作用及其机制研究[J].转化医学杂志,2020,9(5):257-261
EZH2蛋白在非小细胞肺癌顺铂耐药中的作用及其机制研究
Research on the role of EZH2 protein in mechanism of cisplatin resistance in non-small cell lung cancer
  
DOI:
中文关键词:  Zeste基因增强子同源物2蛋白  肺癌  耐药性  细胞凋亡  细胞周期
英文关键词:Enhancer of zeste homolog 2 (EZH2) protein  Lung cancer  Drug-resistance  Apoptosis  Cell cycle
基金项目:国家自然科学基金(81160253);内蒙古自治区肿瘤生物治疗协同创新培育中心项目(1619002010);内蒙古自然科学基金(2017MS0830)
作者单位
齐慧 内蒙古医科大学附属医院血液内科 
呼群 内蒙古医科大学附属医院肿瘤内科 
苏乌云 内蒙古医科大学附属医院肿瘤内科 
贾永峰 内蒙古医科大学附属医院病理科 
陈连香 内蒙古医科大学附属医院血液内科 
曹冉华 内蒙古医科大学附属医院肿瘤内科 
乌日罕 内蒙古医科大学附属医院肿瘤内科 
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中文摘要:
      目的探讨Zeste基因增强子同源物2(enhancer of zeste homolog 2,EZH2)蛋白在非小细胞肺癌对顺铂耐药中的作用及其调控机制。方法采用实时荧光定量PCR(real-time quantitative PCR,qRT-PCR)检测人肺腺癌细胞株A549及其顺铂耐药株A549/DDP中EZH2、P21、Puma和Bad的mRNA表达差异。采用RNA干扰技术抑制细胞中的EZH2蛋白表达。通过细胞毒性实验检测细胞耐药性的改变。qRT-PCR检测抑制EZH2蛋白表达后A549/DDP细胞中P21、Puma和Bad的表达变化。流式细胞仪检测细胞周期的分布和变化。结果EZH2在A549/DDP中呈高表达。抑制EZH2蛋白表达后,顺铂对A549/DDP的IC50由(34.57±3.70)μmol/L降低至(18.91±2.07)μmol/L(P<0.05);抑制EZH2蛋白表达后,A549/DDP中P21、Puma和Bad的mRNA表达均上调;抑制A549/DDP细胞EZH2蛋白表达后,G0/G1期细胞比例下降,G2/M期细胞增多(P<0.05),细胞发生G2/M期阻滞。结论EZH2蛋白参与介导了A549/DDP对顺铂的耐药;EZH2蛋白可能通过调控与细胞凋亡相关基因相关的凋亡通路诱导A549/DDP对顺铂的耐药;EZH2蛋白可能通过抑制P21表达、促进细胞周期进展及肿瘤增殖能力,诱导非小细胞肺癌对顺铂产生耐药。
英文摘要:
      Objective To investigate the role and regulatory mechanism of zeste homolog 2 (EZH2) protein in cisplatin resistance in non-small cell lung cancer. MethodsThe expression difference of EZH2, P21, Bad and Puma mRNA between A549 and A549/DDP was detected by real-time quantitative PCR. siRNA was used for silencing gene expression of EZH2. Assessment of chemoresistance to cisplatin in A549 /DDP cells was performed evaluated by CCK-8 assay. The expression of P21, Bad and Puma mRNA in A549/DDP of EZH2 silenced was detected by realtime quantitative PCR. Cell cycle was analyzed by flow cytometry. ResultsExpression of EZH2 mRNA was overexpressed in A549/DDP compared with A549. Silencing EZH2 expression decreased IC50 of A549/DDP from(34.57±3.70)μmol/L to(18.91±2.07)μmol/L (P<0.05). Inhibiting EZH2 protein expression upregulated expression of P21, Puma, Bad mRNA in A549/DDP. Inhibiting EZH2 protein expression caused percentage decline of G0/G1 phase, and a rise of G2/M phase (P<0.05). Cells was arrested in G2/M phase. ConclusionEZH2 protein is involved in mediating the cisplatin resistance to A549/DDP. EZH2 protein may regulate the pathway of apoptosis to induce A549/DDP resistance to cisplatin. EZH2 protein can inhibit expression of P21, promote cell cycle progression of tumor proliferation and enhance resistance to cisplatin in non-small cell lung cancer.
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