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

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Abstract

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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Abbreviations

ARTs:

Artemisinin and its derivatives

ART:

Artesunate

CPT:

Camptothecin

DHA:

Dihydroartemisinin

DOX:

Doxorubicin

HSPs:

Heat shock proteins

HSP27:

Heat shock protein beta-1

IEF:

Isoelectric focusing

MALDI-TOF MS:

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

MDR:

Multi-drug resistance

MRP1:

MDR-associated protein 1

P-gp:

P-glycoprotein

PI:

Propidium iodide

SRB:

Sulforhodamin B

2-DE:

Two-dimensional gel electrophoresis

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Acknowledgments

This work was partially supported by the National Natural Science of China (No. 81001450). We greatly thank Prof. Ying Li for providing artesunate and Dr. Yi Jiang, Mr. Lin-Jiang Tong for the technical help.

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Authors and Affiliations

  1. College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People’s Republic of China

    Jin-Jian Lu

  2. Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institutes of Materia Medica, Chinese Academy of Science, Shanghai, 201203, People’s Republic of China

    Jin-Jian Lu, Si-Meng Chen, Jian Ding & Ling-Hua Meng

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  1. Jin-Jian Lu
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  2. Si-Meng Chen
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  3. Jian Ding
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  4. Ling-Hua Meng
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Correspondence to Jian Ding or Ling-Hua Meng.

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Lu, JJ., Chen, SM., Ding, J. et al. Characterization of dihydroartemisinin-resistant colon carcinoma HCT116/R cell line. Mol Cell Biochem 360, 329–337 (2012). https://doi.org/10.1007/s11010-011-1072-2

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  • DOI: https://doi.org/10.1007/s11010-011-1072-2

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