EFFECACY OF ANTISENSE OLIGONUCLEOTIDE HUSH-11 WITH THIOPHOSPHATE IN TREATMENT OF MELANOMA IN MICE
Melanoma is one of the highly aggressive cancer diseases. Melanoma accounts for about 2% of the total cancer incidence in Russia. In a large number of cases, melanoma shows its potential to metastasize and becomes a cause of death. Aims. Our research team focused on the design and development of an...
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Published in | Cardiometry no. 24; pp. 40 - 41 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Moscow
Russian New University
30.11.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Melanoma is one of the highly aggressive cancer diseases. Melanoma accounts for about 2% of the total cancer incidence in Russia. In a large number of cases, melanoma shows its potential to metastasize and becomes a cause of death. Aims. Our research team focused on the design and development of an anti-melanoma drug based on antisense oligonucleotides (ASOs) with thiophosphate for the use both in the postsurgery treatment and the targeted therapy. Results. Our pilot experiments showed the effectiveness of blocking the enzyme glucose-6- phosphate dehydrogenase (G6PD) using the thiophosphate antisense oligonucleotide Hush-11, which significantly reduced the cell index in the cancer cells in the cell culture of the Clone M3 melanoma murine line. The measurements were taken with the xCELLigence RTCA DP Analyzer. The determination of the cell index was carried out in 10 repetitions of the experiments performed in real time within 24 hours. The most active action made by the antisense oligonucleotide Hush-11 (5'-AGC-TAT-CTC-CG-3'), at a concentration of 7000 ng per 6000 cells, was observed 8 hours after the beginning of the experiment. The cell index in the reference sample was 0.2680 ± 0.092 s.u. that exceeded the average values in the experimental group by 70.1 ± 1.84% (p <0.01). Thus, our studies demonstrated the inhibitory effect produced by the antisense oligonucleotide Hush-11 on the proliferative activity of the Clone M3 melanoma cells. In addition, an injection of the antisense oligonucleotide Hush-11 into mice with the inoculated Clone M3 melanoma resulted in the significant tumor reduction compared to the untreated reference group. The average tumor size in the groups at the beginning of the experiment was 0.26 ± 0.03 cm2 ; on day 7 of the experiment, significant differences were observed between the mean tumor area recorded in the reference group (0.32 ± 0.07 cm2 ) and the group receiving Hush-11 (0.14 ± 0.04 cm2 ) (p <0.05). Currently, an ointment base formula is being developed for locoregional tumor therapy in order to avoid injections as a possible damaging factor near the tumor that may induce dissemination of cancer cells. Conclusion. The studies showed that in vitro the ASO Hush-11 significantly reduced the cell index in the melanoma cells compared to that in the reference group. The use of ASO Hush-11 in experiments in vivo contributed to a reduction in the tumor size within 7 days. |
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ISSN: | 2304-7232 |
DOI: | 10.18137/cardiometry.2022.24.conf.21 |