Afuresertib (AFU), a novel inhibitor of the serine/threonine kinase AKT, has clinical efficacy as a monotherapy against hematological malignancies and is expected to be used in combination with standard therapies for multiple myeloma (MM).
Higher level of TGF-β was observed in MM-BMSC co-cultured medium (<i>P</i> < 0.001), and down-regulated by PT-100 (<i>P</i> = 0.038). p-AKT was upregulated as compared to T-cells without MM-BMSCs (<i>P</i> = 0.021).
Several proapoptotic genes (AKT1 and AKT2) were down-regulated and antiapoptotic genes (APAF1 and BCL2L1) were up-regulated in multiple myeloma, both symptomatic and asymptomatic, compared to monoclonal gammopathy of undetermined significance.
Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo.
These results demonstrated that the states of phosphorylation of Cyp A by Akt can influence the progress of the cell cycle in MM U266 cells and that this effect is probably mediated through the Janus-activated kinase 2/STAT3 signalling pathway.
So, we supposed that EphA4 interacted with CDK5 and promoted its expression which in turn enhanced p-AKT expression and promoted cell adhesion-mediated drug resistance in multiple myeloma.
The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is such a pathway that is aberrantly activated in a large proportion of MM patients through numerous mechanisms and can play a role in resistance to several existing therapies making this a central pathway in MM pathophysiology.
We conducted a screen to identify other pathways that affect GILZ regulation and report that inhibitors of PI3-kinase/AKT enhanced GILZ expression in MM cell lines and clinical samples.
Taken together, this research supports the first evidence that lncRNA OIP5-AS1 loss-induced miR-410 accumulation facilitates cell proliferation, cycle progression and apoptosis inhibition by targeting KLF10 via activating PTEN/PI3K/AKT pathway in MM.
In view of the significant role of AKT in MM, the allosteric AKT inhibitor MK2206 was selected in order to enhance the antitumor effects of bufalin in different MM cell lines (NCI-H929, U266, LP-1 and RPMI8226).
This novel miR-19a/PTEN/AKT axis sheds new light on the mechanisms underlying apoptosis and invision and may provide potentially therapeutic targets for the treatment of myeloma.
It was observed that FT enhanced the apoptosis caused by bortezomib (Bor) and mitigated proliferation in MM cells, and these events are regulated by nuclear factor-κB (NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, and activator protein-1 (AP-1) activation.
Furthermore, our results demonstrated that the enforced expression of miR-145 in H929 cells profoundly decreased the levels of p-AKT and p-PI3K, which may contribute to some extent to the inhibition of MM cell proliferation and survival.
Here, we show that MLN4924, a potent NEDD8 activating enzyme (NAE) inhibitor, induced cytotoxicity in MM cell lines, and its antitumor effect is associated with suppression of the AKT and mammalian target of rapamycin (mTOR) signaling pathways through increased expression of REDD1.
These results indicate that activation of the AKT kinase is a characteristic of MM cells and suggest that AKT activity is important for MM cell expansion.
The results of Western blot assay showed that the PI3K/AKT/mTOR signaling pathway was activated in bone marrow specimens of patients with MM. miR-215-5p was found to negatively correlate with runt-related transcription factor 1 (RUNX1) expression in MM clinical bone marrow samples.