Gefitinib enhances arsenic trioxide (AS2O3)-induced differentiation of acute promyelocytic leukemia cell line.
Gefitinib (Iressa, ZD1839), a selective epidermal growth factor receptor tyrosine kinase inhibitor, inhibits growth, invasion and colony formation of various cancer cells. However, little is known about the effect of combination of gefitinib and arsenic trioxide (ATO) on differentiation of acute promyelocytic leukemia (APL). Therefore, we investigated whether gefitinib had any role in the ATO-induced differentiation of NB4 cells (APL cell line). Gefitinib induced the expression of differentiation markers including CD11b and CD14 in ATO-treated NB4 cells and facilitated ATO-induced morphologic changes and ROS generation. The results were evident that the combination of gefitinib and ATO could induce more effectively the functional differentiation of leukemic cells to macrophage-like cells. Moreover, the ERK pathway was necessary for the enhancement of gefitinib in ATO-induced differentiation, measured by CD11b and CD14 expression on NB4 cells. Therefore, our data indicated that gefitinib can play a potential role as an adjunctive differentiation agent in APL.
Biomedical Research Center and Division of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714, Republic of Korea.
Eui-Kyu
EK
Noh
Hawk
H
Kim
Min Jae
MJ
Park
Jin Ho
JH
Baek
Jae-Hoo
JH
Park
Seung Joo
SJ
Cha
Jong-Ho
JH
Won
Young Joo
YJ
Min
D000971:Antineoplastic Combined Chemotherapy Protocols; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use
D001152:Arsenicals; D010087:Oxides; D011799:Quinazolines; D048049:Extracellular Signal-Regulated MAP Kinases; D000077156:Gefitinib; D000077237:Arsenic Trioxide