GQIcombi application to subdue glioma via differentiation therapy

Modern therapy approaches fail to prevent high grade glioma recurrence. So, alternative ways need to be developed. Changing glioma cells' fate is an alternative way to prevent tumor growth. Two-step protocol based on an antiproliferative G-quadruplex and small molecules triggering neural differentiation showed to be effective on glioblastoma cell cultures. This approach was named a differential therapy. In this paper, we broaden the spectrum of cell cultures to gliomas of II, III and IV grades, showing the universality of suggested protocol on a variety of cancer cells. We checked the reasonability of consistent addition of factors to the glioma cells. Moreover, we demonstrated a significant inhibition of tumor growth after injection of GQIcombi into 101/8 tumor in glioma rat model. Thus, the proposed strategy of influencing on cancer cell growth is applicable to be further translated for therapy use. Overall design: To investigate the influence of combination of an antiproliferative aptamer and neuroinducing small molecules - GQIcombi - on glioma cell culture of IV Grade, we sequentially added these factors to cells and collected cells for transcriptomic analisys on the 10th day of the experiment.