Therapeutic combination silencing VEGF and SOX10 increases the antiangiogenic effect in the mouse melanoma model B16-F10 - and studies.

INTRODUCTION

Gene therapy is an innovative form of treatment of genetic diseases, in which psiRNA molecules silencing specific genes are applied.

AIM

The study evaluated the anti-tumour effect of psiRNA silencing preparations of the vascular endothelial growth factor (VEGF) and Sry-related HMG-Box gene 10 (SOX10) on melanoma (B16-F10) by inhibiting angiogenesis.

MATERIAL AND METHODS

The preparations based on plasmid vectors psiRNA silencing the gene and that form complexes with cationic lipid (psiRNA/carrier) have been developed. psiRNA preparations were tested on the mouse melanoma cell line B16-F10, both and . The silencing activity of transfected melanoma cells with the obtained psiRNA preparations was examined using the qPCR and Western blot methods. The anti-tumour activity of psiRNA preparations on melanoma tumour cells was then evaluated in a mouse model.

RESULTS

studies have shown that the B16-F10 cells efficiently transfect non-viral preparations - psiRNA: Lyovec (74-89%). Worth mentioning is the fact that silencing in B16-F10 melanoma cells increases the expression of the gene (compared to the preparation inhibiting only ), which codes the endostatin to stop angiogenesis. results show that the level of haemoglobin in tumours of mice treated with psiRNA formulations was over 6 times lower than controls and tumour mass was 60-80% lower.

CONCLUSIONS

The novel study proves that simultaneous inhibition of SOX10 and VEGF enhances the antiangiogenic action and thus contributes to a significant halt of disease development. In addition, these data expand knowledge about SOX10 regulation and functions.