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Arsenic Trioxide overcomes cell adhesion-mediated drug resistance through down-regulating the expression of beta(1)-integrin in K562 chronic myelogenous leukemia cell line
- Source :
- Leukemialymphoma. 51(6)
- Publication Year :
- 2010
-
Abstract
- The bone marrow microenvironment protects leukemia cells from drug-induced damage, and cell adhesion-mediated drug resistance (CAM-DR) is the main obstacle for the eradication of bone marrow minimal residual disease. In this study, we evaluated the survival response of K562 cells co-cultured with bone marrow stromal cells (BMSCs) derived from patients with chronic myelogenous leukemia (CML). Co-cultured K562 cells had a survival advantage after exposure to cytotoxic drugs compared to suspended K562 cells, but there was no survival difference between the two groups following exposure to As(2)O(3). The cytotoxicity of As(2)O(3) combined with cytotoxic drugs had an additive effect in the suspension group and a synergistic effect in the co-cultured group. Similar apoptotic responses were found using flow cytometry assays. As(2)O(3) treatment caused a dose dependent reduction of the adhesion ability of K562 cells to BMSCs, and Western blot analysis revealed that the treatment of K562 cells with As(2)O(3) led to down-regulation of beta(1)-integrin.
- Subjects :
- Cancer Research
Stromal cell
Cell Survival
Blotting, Western
Down-Regulation
Antineoplastic Agents
Apoptosis
Bone Marrow Cells
Biology
Pharmacology
Arsenicals
Myelogenous
Inhibitory Concentration 50
Arsenic Trioxide
hemic and lymphatic diseases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
medicine
Cell Adhesion
Cytotoxic T cell
Humans
Cells, Cultured
Dose-Response Relationship, Drug
Integrin beta1
Daunorubicin
Cytarabine
Drug Synergism
Oxides
Hematology
medicine.disease
Minimal residual disease
Coculture Techniques
Leukemia
medicine.anatomical_structure
Oncology
Drug Resistance, Neoplasm
Cancer research
Bone marrow
Stromal Cells
K562 Cells
Chronic myelogenous leukemia
K562 cells
Subjects
Details
- ISSN :
- 10292403
- Volume :
- 51
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Leukemialymphoma
- Accession number :
- edsair.doi.dedup.....8bc51997b3cae6c329a22a96c1b7f6fc