Inhibition of IGF-1 Signalling Enhances the Apoptotic Effect of AS602868, an IKK2 Inhibitor, in Multiple Myeloma Cell Lines

被引：17
作者：
Tagoug, Ines [1 ,2 ,3 ,4 ]
De Chalon, Amelie Sauty [1 ,2 ,3 ,4 ]
Dumontet, Charles [1 ,2 ,3 ,4 ]
机构：
[1] Univ Lyon, Lyon, France
[2] Ctr Rech Cancerol Lyon, INSERM, U1052, Lyon, France
[3] Ctr Rech Cancerol Lyon, CNRS, UMR 5286, Lyon, France
[4] HCL, Lyon, France
来源：
PLOS ONE | 2011年 / 6卷 / 07期
关键词：
GROWTH-FACTOR-I; FACTOR-KAPPA-B; RECEPTOR KINASE INHIBITOR; CONSTITUTIVE ACTIVATION; TUMOR-GROWTH; MONOCLONAL-ANTIBODY; PATHWAY INHIBITION; LUNG-CANCER; PROLIFERATION; INTERLEUKIN-6;
D O I：
10.1371/journal.pone.0022641
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Multiple myeloma (MM) is a B cell neoplasm characterized by bone marrow infiltration with malignant plasma cells. IGF-1 signalling has been explored as a therapeutic target in this disease. We analyzed the effect of the IKK2 inhibitor AS602868, in combination with a monoclonal antibody targeting IGF-1 receptor (anti-IGF-1R) in human MM cell lines. We found that anti-IGF-1R potentiated the apoptotic effect of AS602868 in LP1 and RPMI8226 MM cell lines which express high levels of IGF-1R. Anti-IGF-1R enhanced the inhibitory effect of AS602868 on NF-kappa B pathway signalling and potentiated the disruption of mitochondrial membrane potential caused by AS602868. These results support the role of IGF-1 signalling in MM and suggest that inhibition of this pathway could sensitize MM cells to NF-kappa B inhibitors.
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页数：9
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