Pim-1 expression and monoclonal antibody targeting in human leukemia cell lines
| Autor: | Jie Li, Pei Xiang Xing, Xiu Feng Hu, Bruce E. Loveland |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Antibodies Neoplasm medicine.drug_class Cell Antineoplastic Agents Apoptosis Mice SCID Biology Monoclonal antibody Mice chemistry.chemical_compound Proto-Oncogene Proteins c-pim-1 In vivo Cell Line Tumor hemic and lymphatic diseases Genetics medicine Animals Humans ATP Binding Cassette Transporter Subfamily B Member 1 Propidium iodide Phosphorylation Molecular Biology Tumor Stem Cell Assay Leukemia Leukemia Experimental Cell growth Antibodies Monoclonal Cell Biology Hematology medicine.disease Xenograft Model Antitumor Assays Molecular biology Neoplasm Proteins Gene Expression Regulation Neoplastic medicine.anatomical_structure Verapamil chemistry Drug Resistance Neoplasm Cell culture bcl-Associated Death Protein Protein Processing Post-Translational |
| Zdroj: | Experimental Hematology. 37:1284-1294 |
| ISSN: | 0301-472X |
| Popis: | Objective Based on our previous findings that Pim-1 was expressed on the cell surface and could be targeted with a highly specific anti–Pim-1 monoclonal antibody (P9), this study aims to evaluate the possibility that Pim-1 could be targeted for the treatment of human leukemia. Materials and Methods Pim-1 expression was investigated in a series of human leukemia cell lines with immunohistochemistry and flow cytometry. The inhibitory effect of P9 on cell proliferation was evaluated with 3 H-thymidine incorporation assay. Cell apoptosis was assayed with Annexin-V/propidium iodide dual staining. The in vivo effect of P9 was evaluated with xenograft tumor models in severe combined immunodeficient mice. Results Pim-1 expression varied depending on the cell lines and correlated with the inhibitory effects mediated by P9. An association between Pim-1 expression and drug resistance was observed. Although the drug-resistant CEM/A7R cells were highly resistant to cytotoxic P-glycoprotein substrates, their growth was inhibited by P9 as demonstrated by in vitro proliferation assay and in vivo inhibition of xenograft tumors. P9 had little effect on P-glycoprotein expression and intracellular Rhodamine 123 accumulation, but it inhibited the phosphorylation of Bad and induced apoptosis. Conclusions Pim-1 is variably expressed in leukemia cell lines and associated with drug resistance. Targeting Pim-1 with monoclonal antibody could be explored for the treatment of leukemia and may represent a novel strategy to overcome drug resistance. |
| Databáze: | OpenAIRE |
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