傅应亚, 韩晓黎, 黎友伦. 抑制JNK信号通路下调A549中LRP表达可增强顺铂化疗敏感性[J]. 中国肿瘤临床, 2013, 40(24): 1518-1522. DOI: 10.3969/j.issn.1000-8179.20131036
引用本文: 傅应亚, 韩晓黎, 黎友伦. 抑制JNK信号通路下调A549中LRP表达可增强顺铂化疗敏感性[J]. 中国肿瘤临床, 2013, 40(24): 1518-1522. DOI: 10.3969/j.issn.1000-8179.20131036
Yingya FU, Xiaoli HAN, Youlun LI. Inhibition of the JNK pathway downregulates lung-resistance protein and enhances the chemosensitivity of A549 cells to cisplatin[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2013, 40(24): 1518-1522. DOI: 10.3969/j.issn.1000-8179.20131036
Citation: Yingya FU, Xiaoli HAN, Youlun LI. Inhibition of the JNK pathway downregulates lung-resistance protein and enhances the chemosensitivity of A549 cells to cisplatin[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2013, 40(24): 1518-1522. DOI: 10.3969/j.issn.1000-8179.20131036

抑制JNK信号通路下调A549中LRP表达可增强顺铂化疗敏感性

Inhibition of the JNK pathway downregulates lung-resistance protein and enhances the chemosensitivity of A549 cells to cisplatin

  • 摘要:
      目的  探讨在顺铂作用下的A549细胞中JNK信号通路与肺耐药蛋白LRP之间的相互关系。
      方法  用SP600125抑制JNK信号通路的活化,CCK-8法检测顺铂药物敏感性,流式细胞术检测细胞凋亡率,用Western blotting法检测LRP、JNK、P-JNK的表达。
      结果  顺铂可活化JNK信号通路,上调LRP的表达;用SP600125抑制JNK信号通路后,LRP的表达下调,增强了顺铂化疗敏感性,促进了细胞凋亡。
      结论  在A549细胞中,活化的JNK信号通路上调LRP的表达促进化疗耐药,因此阻断JNK信号通路为肺癌提供新的治疗靶点。

     

    Abstract:
      Objective  To investigate the relationship between the c-Jun N-terminal kinase (JNK) pathway and lung-resistance protein (LRP).
      Methods  A549 cells were treated with various concentrations of CDDP for 72 h. The LRP mRNA expression was then analyzed using reverse transcription PCR (RT-PCR). LRP, JNK, and P-JNK were analyzed by Western blotting. The A549 cells were then pretreated with SP600125 (2 μg/ml to 4 μg/ml) for 1 h. Afterward, CDDP (16 μg/ml) was added into the culture for 72 h. A Cell Counting Kit-8 was used to investigate the sensitivity of CDDP to the A549 cells. Flow cytometry was used to detect the apoptosis rate. The LRP mRNA expression was analyzed using RT-PCR. LRP, JNK, and P-JNK were analyzed by Western blotting.
      Results  CDDP induced the mRNA and protein expression of both LRP and P-JNK in a dose-dependent manner. Pretreatment with SP600125 enhanced the sensitivity of CDDP to the A549 cells and increased the apoptosis rate. However, the LRP mRNA and LRP expression in the pretreated cells was lower than that in the presence of CDDP alone.
      Conclusion  In A549 cells, CDDP induces the LRP expression via the JNK pathway. This result suggests that lung cancer therapy can be improved by the addition of CDDP to inhibit the JNK signaling pathway.

     

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