Association between sensitivity to L-asparaginase in human cutaneous melanoma cells and asparagine synthetase and glutamine synthetase gene expression

BACKGROUND: L-asparaginase is an enzyme used in clinical practice for the treatment of some blood cancers. It has an antiproliferative effect in some solid tumors. To increase the efficacy of L-asparaginase, it is relevant to identify markers that predict tumor sensitivity to this enzyme. The expression of the ASNS and GLUL genes in tumor cells was previously proposed as such a marker. However, for some tumors, including melanoma, data on the association between the expression of these genes and sensitivity to L-asparaginase are absent or limited.

AIM: The work aimed to assess the association between sensitivity to L-asparaginase in melanoma cells and expression of the ASNS and GLUL genes.

METHODS: The cytotoxicity was assessed using the MTT assay in 35 cell lines. Gene expression was assessed using real-time reverse transcription polymerase chain reaction. The Spearman’s correlation coefficient was used to assess the association between expression and sensitivity.

RESULTS: The calculated IC₅₀ for L-asparaginase in melanoma cell cultures was 0.01–199.91 IU/mL (median: 2.96 IU/mL; arithmetic mean: 16.95 IU/mL). The ASNS gene expression was 0.02–7.38 (median: 0.4; arithmetic mean: 0.98). The GLUL gene expression was 0.06–14.78 (median: 0.64; arithmetic mean: 1.41). The correlation between IC₅₀ and ASNS expression was confirmed by the Spearman’s correlation coefficient of 0.751. There was no correlation between IC₅₀ and GLUL expression (Spearman’s correlation coefficient: 0.077).

CONCLUSION: A positive correlation was confirmed between melanoma cell resistance to L-asparaginase and ASNS gene expression in these cells. A similar correlation for the GLUL gene was not confirmed.