Targeting integrin-linked kinase increases apoptosis and decreases invasion of myeloma cell lines and inhibits IL-6 and VEGF secretion from BMSCs.
In this study, we investigated ILK expression in myeloma cell lines U266 and H929 kept in suspension and cocultured with BMSCs, and studied the pharmacologic inhibitors of ILK on the apoptosis, invasive potential of myeloma cell lines, and production of pro-angiogenic factors of bone marrow stromal cells. We found that ILK protein was expressed in U266 and H929 cells and kinase activity was elevated when cocultured with BMSCs. ILK inhibitor QLT0267 reduced ILK kinase activity and increased apoptosis both in myeloma cell lines kept in suspension and cocultured with BMSCs. ILK inhibition by ILK inhibitor decreased the in vitro invasive capability of myeloma cell lines. In addition, QLT0267 significantly decreased VEGF and IL-6 secretion in BMSCs in a dose-dependent fashion. The results indicated that inhibition of ILK may provide a potential target for myeloma therapy.
Wang
Xiaofang
X
Department of Hematology, Key Laboratory of Cancer Prevention and Therapy, Cancer Hospital of Tianjin, Tianjin Medical University, Tianjin, 300060, People's Republic of China.
Zhang
Zhiqing
Z
Yao
Cheng
C
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001391:Azo Compounds / Q000494:pharmacology; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099200:Scaffold Protein ILK
D001391:Azo Compounds; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D017346:Protein Serine-Threonine Kinases; D011720:Pyrazoles; D042461:Vascular Endothelial Growth Factor A; D000099200:Scaffold Protein ILK; C552362:QLT 0267