PMID- 20470221 OWN - NLM STAT- MEDLINE DCOM- 20100927 LR - 20190116 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 51 IP - 6 DP - 2010 Jun TI - Arsenic Trioxide overcomes cell adhesion-mediated drug resistance through down-regulating the expression of beta(1)-integrin in K562 chronic myelogenous leukemia cell line. PG - 1090-7 LID - 10.3109/10428191003746315 [doi] AB - 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. FAU - Guo-Bao, Wang AU - Guo-Bao W AD - State Key Laboratory of Oncology in South China, Guangzhou, PR China. FAU - Xiao-Qin, Chen AU - Xiao-Qin C FAU - Qi-Rong, Geng AU - Qi-Rong G FAU - Jie, Li AU - Jie L FAU - Gui-Nan, Lin AU - Gui-Nan L FAU - Yue, Lu AU - Yue L LA - eng PT - Journal Article PL - United States TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antineoplastic Agents) RN - 0 (Arsenicals) RN - 0 (Integrin beta1) RN - 0 (Oxides) RN - 04079A1RDZ (Cytarabine) RN - S7V92P67HO (Arsenic Trioxide) RN - ZS7284E0ZP (Daunorubicin) SB - IM MH - Antineoplastic Agents/pharmacology MH - Apoptosis/drug effects MH - Arsenic Trioxide MH - Arsenicals/*pharmacology MH - Blotting, Western MH - Bone Marrow Cells/pathology MH - Cell Adhesion/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Coculture Techniques MH - Cytarabine/pharmacology MH - Daunorubicin/pharmacology MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects MH - Drug Resistance, Neoplasm/*drug effects MH - Drug Synergism MH - Humans MH - Inhibitory Concentration 50 MH - Integrin beta1/*metabolism MH - K562 Cells MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/pathology MH - Oxides/*pharmacology MH - Stromal Cells/drug effects/metabolism/pathology EDAT- 2010/05/18 06:00 MHDA- 2010/09/29 06:00 CRDT- 2010/05/18 06:00 PHST- 2010/05/18 06:00 [entrez] PHST- 2010/05/18 06:00 [pubmed] PHST- 2010/09/29 06:00 [medline] AID - 10.3109/10428191003746315 [doi] PST - ppublish SO - Leuk Lymphoma. 2010 Jun;51(6):1090-7. doi: 10.3109/10428191003746315.