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RNA聚合酶Ⅰ抑制剂通过NF-κb调控鼻咽癌细胞系CNE-1的增殖、侵袭与凋亡

RNA PolymeraseⅠInhibitor Regulates Proliferation, Invasion and Apoptosis of Nasopharyngeal Carcinoma Cell Line CNE-1 by NF-κb

  • 摘要:
    目的 探讨RNA聚合酶Ⅰ抑制剂CX-5461对人鼻咽癌细胞CNE-1增殖、侵袭与凋亡的作用机制。
    方法 免疫组织化学染色检测鼻咽癌与癌旁组织NF-κb的表达。Western blot检测相关效应蛋白在蛋白质水平的表达。CCK-8法检测不同浓度药物处理后CNE-1细胞系的增殖情况。Transwell法比较药物处理后CNE-1细胞系的侵袭能力变化。流式细胞术检测不同浓度药物处理后鼻咽癌细胞系CNE-1细胞周期和凋亡的变化。
    结果 鼻咽癌组织中磷酸化NF-κb表达较癌旁组织明显增高(P < 0.01)。NF-κb总蛋白在蛋白水平无明显变化,但磷酸化水平在药物处理后明显降低(P < 0.01)。Bax较对照组明显增高(P < 0.01),Bcl-2较对照组明显降低(P < 0.01)。药物处理后,发现CNE-1细胞系的增殖、侵袭能力较对照组明显降低且差异具有统计学意义(均P < 0.01);细胞凋亡较对照组明显增多(P < 0.01),药物处理组较对照组细胞周期明显阻滞在G2期(P < 0.01)。
    结论 RNA聚合酶Ⅰ抑制剂CX-5461能够通过调控NF-κb磷酸化促进鼻咽癌CNE-1细胞系凋亡及周期阻滞,抑制其增殖与侵袭能力。

     

    Abstract:
    Objective To investigate the effect of RNA polymerase I inhibitor CX-5461 on the proliferation, invasion and apoptosis of human nasopharyngeal carcinoma cell line CNE-1.
    Methods Immunohistochemical staining was used to determine the difference in phosphorylated NF-κb expression between nasopharyngeal carcinoma and paracancerous tissues. Western blot was used to detect the expression of related effector proteins at the protein level. The CCK-8 method was used to detect the proliferation of CNE-1 cell line treated with different concentrations of drugs. Transwell method was applied to detect the invasive ability of CNE-1 cell line after drug treatment. Flow cytometry was used to detect cell cycle and apoptosis of nasopharyngeal carcinoma cell line CNE-1 treated with different concentrations of drugs.
    Results Immunohistochemical staining showed that the expression of NF-κb in nasopharyngeal carcinoma tissues was significantly higher than that in adjacent tissues (P < 0.01). The total protein of NF-κb did not change significantly at the protein level, but the phosphorylation level and Bcl-2 were significantly decreased, while Bax was significantly increased after drug treatment (all P < 0.01). After drug treatment, the proliferation and invasion abilities of CNE-1 cell line were significantly lower than that of the control group detected by CCK-8 (P < 0.01) and Transwell (P < 0.01); Hoechst fluorescence staining showed that cell apoptosis was significantly higher than that of the control group (P < 0.01); flow cytometry showed that cell cycle of the drug-administered group was significantly blocked in the G2 phase (P < 0.01).
    Conclusion RNA polymerase I inhibitor CX-5461 could promote the apoptosis and cycle arrest, and inhibit the proliferation and invasion abilities of nasopharyngeal carcinoma CNE-1 cell line by regulating NF-κb phosphorylation.

     

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