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Innovative therapeutic strategies



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Published on 14 April 2023
The goal of this research axis is to develop innovative therapeutic strategies targeting microRNAs and CK2 protein kinase in ACC and ccRCC.


Nanovectorization of microRNA inhibitors in adrenocortical carcinoma


Figure 1: Internalization of therapeutic nanoparticles (Lipidots/antimiR complexes) targeting an overexpressed microRNA in adrenocortical carcinoma cells. Visualization by Confocal Microscopy.
Blue = Hoechst (nuclei). Red = Lipidots (lipid nanoparticles). Green = microRNA inhibitor.



Inhibition of the enzymatic activity of protein kinase CK2 by suppression of α2ß2 holoenzyme formation


Figure 2: (a) Crystal structure of CK2 subunits a and b. (b) Zoom on a chemical compound disrupting CK2 subunit interaction (Kufareva, Scientific Reports, 2019).



A combination of kinase inhibitors for the treatment of kidney cancer

 
Figure 3: 3D views of spheroids generated from the ccRCC cell line 786-O (Light sheet fluorescent microscopy).
Blue = Hoechst (nuclei). Green = Phalloidin (Actin). Red = MitoSox (ROS). 		 Figure 4: 786-O spheroids were treated for 24 h with 5 µM of CX-4945 (CK2 inhibitor) and 10 µM of KU-60019 (ATM inhibitor), in the presence of MitoSox (5 µM) to visualize the production of ROS inducing cell death.
Blue = Hoechst. Green = Phalloidin. Red = MitoSox.



Figure 5: Effect of CX-4945 (CK2 inhibitor) and KU-60019 (ATM inhibitor) on tumor cell viability. Tissue slices carrying tumor and normal kidney tissue obtained from a patient with ccRCC (COMBOREIN project) were marked using Live and Dead assay after 48h of treatments with (a) Vehicle (b) KU-60019 10 μM (c) CX-4945 10 μM and (d) KU 10 μM + CX 10 μM. Measurement of propidium iodide intensity (Red marker = dead cells) in both normal and tumor areas revealed a significant increase in dead cells after treatment with KI and CX combination. (Green marker calcein = lived cells).