Statins inhibited the MIP-1α expression via inhibition of Ras/ERK and Ras/Akt pathways in myeloma cells

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Masanobu TsubakiShozo Nishida

Abstract

Macrophage inflammatory protein-1alpha (MIP-1α) is detected at high concentrations in patients with multiple myeloma. It is thought to play an important role in the etiology of multiple myeloma and osteolysis. Thus, inhibiting MIP-1α expression may be useful in developing therapeutic treatments for multiple myeloma-induced osteolysis. In this study, we investigated the potential of statins to inhibit mRNA expression and secretion of MIP-1α in mouse myeloma cells (MOPC-31C). We found that statins inhibited the lipopolysaccharide (LPS)-induced MIP-1α mRNA expression and protein secretion in MOPC-31C cells. This inhibition was reversed when farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), intermediates of the mevalonate pathway, were combined with statins. Furthermore, statins reduced the GTP form of Ras, a phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated Akt. Our results indicate that statins inhibit biosynthesis of FPP and GGPP and thereby down regulate signal transduction of Ras/ERK and Ras/Akt pathways. The net effect suppresses LPS-induced MIP-1α mRNA expression and protein secretion in MOPC-31C cells. Thus, statins hold great promise for developing effective therapies...Continue Reading

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Citations

Oct 11, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Daichiro FujiwaraShozo Nishida
Dec 18, 2019·ANZ Journal of Surgery·Dimitrios KaraviasUNKNOWN Nottingham HPB Surgery Group
Oct 15, 2019·Experimental Lung Research·Hwa Young LeeJi Young Kang
Dec 29, 2020·Trends in Cancer·Dennis Juarez, David A Fruman
Oct 30, 2020·International Journal of Molecular Sciences·Masanobu TsubakiShozo Nishida

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