Arsenic Trioxide overcomes cell adhesion-mediated drug resistance through down-regulating the expression of β₁-integrin in K562 chronic myelogenous leukemia cell line

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 As₂O₃. The cytotoxicity of As₂O₃ 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. As₂O₃ 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 As₂O₃ led to down-regulation of β₁-integrin.

Keywords:

• As₂O₃
• chronic myelogenous leukemia
• β₁-integrin
• drug resistance

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.