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https://doi.org/10.14300/mnnc.2025.20035

Prospects of targeted therapy for skin melanoma: pronounced apoptotic effect of the Skeen-11 antisense oligonucleotide on G6PD gene expression

[Experimental medicine]
Ksenia Andreevna Yurchenko; Vladimir Vladimirovich Oberemok; Anatoly Vladimirovich Kubyshkin;

Melanoma still remains a highly aggressive pathology with an uncertain prognosis. Compared to other tumor processes, the range of pharmacotherapeutic technologies available for combating melanoma is rather limited.

Antisense oligonucleotides (ASO) capable of specifically binding to target molecules, thus limiting their functional capacity, are regarded as one of the promising pathogenetic methods to be employed to treat skin melanoma.

The study presented here offers the results of possible suppressing G6PD activity by Skeen-11 thiophosphate ASO using a model of the Clone M-3 mouse melanoma cell line. The study implied identifying the cell viability, the apoptosis level, the activity of metabolic enzymes, and the expression of the G6PD gene following exposure to Skeen-11, while using conventional cytometric, biochemical, and molecular biological methods.

Skeen-11 ASO has been shown to dose-dependently regulate the G6PD gene expression, to inhibit the NADH dehydrogenase complex, as well as to have a significant cytotoxic, apoptotic effect in Clone M-3 cells. The obtained outcomes serve proof to the promising potential of further Skeen-11 study as a molecular basis for the development of newer therapies for skin melanoma.

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Keywords: antisense oligonucleotides, melanoma cells, G6PD, targeted therapy, gene expression