title: Characterization of dihydroartemisinin-resistant colon carcinoma HCT116/R cell line.
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.
authors.affiliation: College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Jin-Jian
authors.initials: JJ
authors.lastname: Lu
authors.forename: Si-Meng
authors.initials: SM
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Ling-Hua
authors.initials: LH
authors.lastname: Meng
mesh_terms: D017302:Annexins / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D000077332:Artesunate; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D045325:HCT116 Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D017302:Annexins; D000970:Antineoplastic Agents; D037621:Artemisinins; D006360:Heat-Shock Proteins; D000077332:Artesunate; C039060:artenimol; D010751:Phosphopyruvate Hydratase