Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia

被引：17

作者：

Alessandro, Riccardo ^{[1
]}

Fontana, Simona ^{[1
]}

Giordano, Margherita ^{[1
]}

Corrado, Chiara ^{[1
]}

Colomba, Paolo ^{[1
]}

Flugy, Anna Maria ^{[1
]}

Santoro, Alessandra ^{[2
]}

Kohn, Elise C. ^{[3
]}

De Leo, Giacomo ^{[1
]}

机构：

[1] Univ Palermo, Dipartimento Biopatol & Metodol Biomed, Sezione Biol & Genet, I-90133 Palermo, Italy

[2] Dipartimento Ric Clin & Biotecnol AO V Cervello, Lab Ematol, Palermo, Italy

[3] NCI, Ctr Canc Res, Pathol Lab, Mol Signalling Sect, Bethesda, MD 20892 USA

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2008年 / 215卷 / 01期

关键词：

D O I：

10.1002/jcp.21290

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Although imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML), some patients develop resistance with progression of leukemia. Alternative or additional targeting of signaling pathways deregulated in bcr-abl-driven CML cells may provide a feasible option for improving clinical response and overcoming resistance. In this study, we show that carboxyamidotriazole (CAI), an orally bioavailable calcium influx and signal transduction inhibitor, is equally effective in inhibiting the proliferation and bcr-abl dependent- and independent-signaling pathways in imatinib-resistant CML cells. CAI inhibits phosphorylation of cellular proteins including STATS and CrkL at concentrations that induce apoptosis in IM-resistant CML cells. The combination of imatinib and CAI also down-regulated bcr-abl protein levels. Since CAI is already available for clinical use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of CML.

引用

页码：111 / 121

页数：11

共 52 条

[1] Endothelial cell spreading on type IV collagen and spreading-induced FAK phosphorylation is regulated by Ca2+ influx [J].