eISSN: 2299-0046
ISSN: 1642-395X
Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii
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SCImago Journal & Country Rank
5/2021
vol. 38
 
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abstract:
Original paper

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

Joanna Bogusławska-Duch
1
,
Magdalena Ducher-Hanaka
1
,
Agnieszka Zajkowska
1
,
Milena Czajka
1
,
Maciej Małecki
1

1.
Department of Applied Pharmacy, Medical University of Warsaw, Warsaw, Poland
Adv Dermatol Allergol 2021; XXXVIII (5): 887–898
Online publish date: 2021/11/05
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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 SOX10 and VEGF that form complexes with cationic lipid (psiRNA/carrier) have been developed. psiRNA preparations were tested on the mouse melanoma cell line B16-F10, both in vitro and in vivo. 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 in vivo model.

Results
In vitro studies have shown that the B16-F10 cells efficiently transfect non-viral preparations – psiRNA: Lyovec (74–89%). Worth mentioning is the fact that silencing SOX10 in B16-F10 melanoma cells increases the expression of the COL18A1 gene (compared to the preparation inhibiting only VEGF), which codes the endostatin to stop angiogenesis. In vivo 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.

keywords:

cancer, melanoma, vascular endothelial growth factor, Sry-related HMG-Box gene 10, gene therapy, angiogenesis

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