基础医学与临床 ›› 2019, Vol. 39 ›› Issue (6): 821-825.

• 研究论文 • 上一篇    下一篇

HSP90靶向抑制剂P7与阿霉素联用对急性髓性白血病细胞凋亡的协同增效作用

王俊1,张逸2,曹明月1,黄薇3,杨楠3,刘雁勇3   

  1. 1. 中国医学科学院北京协和医学院基础医学研究所
    2. 中国医学科学院基础医学研究所
    3. 中国医学科学院基础医学研究所,北京协和医学院基础学院
  • 收稿日期:2019-02-25 修回日期:2019-04-17 出版日期:2019-06-05 发布日期:2019-06-04
  • 通讯作者: 刘雁勇 E-mail:yanyongliu@ibms.pumc.edu.cn
  • 基金资助:
    中国医学科学院医学与健康科技创新工程;北京市自然科学基金;协和青年科研基金与中央高校基本科研业务费专项基金

Synergistic antitumor effect of HSP90 targeted inhibitor peptide P7 combined with doxorubicin in acute myeloid leukemia cells apoptosis

  • Received:2019-02-25 Revised:2019-04-17 Online:2019-06-05 Published:2019-06-04
  • Contact: yong YanLIU E-mail:yanyongliu@ibms.pumc.edu.cn

摘要: 目的 探讨热休克蛋白HSP90靶向抑制多肽LPLTPLP(P7)与临床标准化疗药物阿霉素(DOX)联用对急性髓性白血病细胞系NB4的影响。方法 多肽P7与DOX单药或两药联合处理NB4细胞系48 h后,CCK-8法检测细胞的存活,并用等效图解法解析其作用;流式细胞计量术检测NB4细胞凋亡水平;蛋白免疫印迹检测NB4细胞凋亡蛋白PARP的表达水平及剪切水平。结果 P7与DOX对细胞存活具有协同抑制作用;P7与DOX联合用药组细胞凋亡率为63.9%,约等于P7和DOX两药单独用药时凋亡率之和;两药联用组凋亡相关蛋白PARP总蛋白表达显著下调(P<0.01),cleaved-PARP的水平显著上调(P<0.01)。结论 P7协同DOX能显著提高NB4细胞的凋亡比例,其机制可能与凋亡相关蛋白PARP的激活有关。

关键词: 急性髓性白血病, 细胞凋亡, 阿霉素, 多肽, 协同作用

Abstract: Objective To explore the effect of doxorubicin (DOX) combined with a Heat shock protein 90 targeted heptapeptide - LPLTPLP (P7) in the acute myeloid leukemia cell line NB4 in vitro. Methods Following treatment with P7, DOX, or P7 combined with DOX fin NB4 cells for 48 h, cell viability was assessed by CCK-8 assay and analysis with the isobologram method;Flow cytometry was carried out to quantify apoptotic cells;The expression and cleavage level of PARP protein were investigated by Western blot analysis. Results P7 synergized with DOX for inhibiting cell viability. The apoptotic rate of combination of P7 and DOX was approximately equal to the sum of P7 and DOX apoptotic rate. The protein expression of PARP was significantly decreased while that of cleaved PARP was significantly increased with the treatment of P7 or/and DOX. Conclusions Combination of P7 and DOX exhibits synergistic effects on NB4 cells by increasing apoptosis rate, the mechanism of which may be associated with the activation of apoptosis-related protein PARP.

Key words: Acute myeloid leukemia, Apoptosis, Doxorubicin, Heptapeptide, synergy

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