Characterization of dihydroartemisinin-resistant colon carcinoma HCT116/R cell line

Characterization of dihydroartemisinin-resistant colon carcinoma HCT116/R cell line
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双氢青蒿素耐药结肠癌HCT116/R细胞系的表征

DOI:
10.1007/s11010-011-1072-2
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发表时间:
2011
影响因子:
4.3
通讯作者:
Meng, Ling-Hua
Meng, Ling-Hua
中科院分区:
生物学3区
文献类型:
--
作者:
Lu, Jin-Jian;Chen, Si-Meng;Ding, Jian;Meng, Ling-Hua

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双氢青蒿素(DHA)是青蒿素的重要衍生物,具有很强的抗肿瘤活性。本实验室前期从结肠癌细胞系HCT 116中建立了一株对DHA耐药的细胞系HCT 116/R。在此,我们发现,HCT 116/R细胞更耐DHA或青蒿琥酯诱导的增殖抑制和更耐受DHA诱导的细胞周期阻滞和凋亡相比,父母HCT 116细胞。在两种细胞系中,P-糖蛋白和MDR相关蛋白1的蛋白水平以及细胞中多柔比星的蓄积相似。此外,HCT 116/R细胞对喜树碱和阿霉素诱导的细胞生长抑制仍然敏感。为了进一步探索HCT 116/R细胞系的特征,采用双向凝胶电泳和基质辅助激光解吸/电离飞行时间质谱进行蛋白质组学研究。这不仅表明暴露于DHA可能不会诱导肿瘤多药耐药表型,但也提供了新的线索,进一步研究DHA和其他青蒿素衍生物的抗癌机制。
Dihydroartemisinin (DHA) is an important artemisinin derivative and presents profound anti-tumor potential. A DHA-resistant cell line named HCT116/R derived from colon carcinoma cell line HCT116 was established in our previous study. Herein, we found that HCT116/R cells were much more resistant to DHA- or artesunate-induced proliferation inhibition and more tolerant to DHA-induced cell cycle arrest and apoptosis compared with those of the parent HCT116 cells. The protein levels of P-glycoprotein and MDR-associated protein 1 and the accumulation of doxorubicin in cells were similar in both cell lines. Moreover, HCT116/R cells were still sensitive to camptothecin- and doxorubicin-induced cell growth inhibition. To further explore the characterization of HCT116/R cell line, a proteomic study employing two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was performed. Eight different expressed proteins between the two cell lines were identified including some heat shock proteins, annexins, etc. This study not only indicates that exposure to DHA may not induce a tumor multi-drug-resistant phenotype but also affords new clues for the further investigation of the anti-cancer mechanisms of DHA and other artemisinin derivatives.
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