Background:
Ruxolitinib is a selective JAK1/2 inhibitor approved by FDA for myelofibrosis in 2014 and nowadays, comprehensive investigations on the potential of the agent as a targeted therapy for haematological malignancies are on the rise. In multiple myeloma which is a cancer of plasma cells, Interleukin-6/JAK/STAT pathway is emerging as a therapeutic target since the over activation of the pathway is associated with poor prognosis.
Objective:
In this study, our purpose was to discover the potential anticancer effects of ruxolitinib in ARH-77 multiple myeloma cell line compared to NCI-BL 2171 human healthy B lymphocyte cell line.
Methods:
Cytotoxic effects of ruxolitinib in ARH-77 and NCI-BL 2171 cells were determined via WST-1 assay. Investigation of the autophagy mechanism induced by ruxolitinib measured by detecting autophagosome formation. Apoptotic effects of ruxolitinib were analyzed with Annexin V‐FITC Detection Kit and flow cytometry. We performed RT-qPCR to demonstrate the expression changes of the genes in IL-6/JAK/STAT pathway in ARH-77 and NCI-BL 2171 cells treated with ruxolitinib.
Results:
We identified the IC50 values of ruxolitinib for ARH-77 and NCI-BL 2171 as 20.03 and 33.9μM at the 72th hour, respectively. We showed that ruxolitinib induced autophagosome accumulation by 3.45 and 1.70 folds in ARH-77 and NCI-BL 2171 cells compared to control group, respectively. Treatment with ruxolitinib decreased the expressions of IL-6, IL-18, JAK2, TYK2 and, AKT genes which play significant roles in MM pathogenesis.
Conclusion:
All in all, ruxolitinib is a promising agent for the regulation of IL-6/JAK/STAT pathway and interfering with autophagy mechanism in MM.
Extracellular matrix
(ECM)-derived hydrogels are in demand for
use in lung tissue engineering to mimic the native microenvironment
of cells in vitro. Decellularization of native tissues has been pursued
for preserving organotypic ECM while eliminating cellular content
and reconstitution into scaffolds which allows re-cellularization
for modeling homeostasis, regeneration, or diseases. Achieving mechanical
stability and understanding the effects of the decellularization process
on mechanical parameters of the reconstituted ECM hydrogels present
a challenge in the field. Stiffness and viscoelasticity are important
characteristics of tissue mechanics that regulate crucial cellular
processes and their in vitro representation in engineered models is
a current aspiration. The effect of decellularization on viscoelastic
properties of resulting ECM hydrogels has not yet been addressed.
The aim of this study was to establish bovine lung tissue decellularization
for the first time via pursuing four different protocols and characterization
of reconstituted decellularized lung ECM hydrogels for biochemical
and mechanical properties. Our data reveal that bovine lungs provide
a reproducible alternative to human lungs for disease modeling with
optimal retention of ECM components upon decellularization. We demonstrate
that the decellularization method significantly affects ECM content,
stiffness, and viscoelastic properties of resulting hydrogels. Lastly,
we examined the impact of these aspects on viability, morphology,
and growth of lung cancer cells, healthy bronchial epithelial cells,
and patient-derived lung organoids.
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