Email this article Chemoresistance of PRAME-expressing melanoma cell can be resolved with help of bortezomib
- Authors: Misyurin V.A.1, Kalenichenko D.V.2, Rudakova A.A.1, Finashutina Y.P.1, Lyzhko N.A.1, Tikhonova V.V.1, Kesaeva L.A.1, Solopova O.N.1, Misyurina A.Е.3, Velikanov A.N.4, Baryshnikovа M.А.1, Misyurin A.V.1
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Affiliations:
- N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
- K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology
- National Research Center for Hematology, Ministry of Health of Russia
- M.V. Lomonosov Moscow State University
- Issue: Vol 5, No 4 (2018)
- Pages: 131-134
- Section: SHORT REPORTS
- Published: 04.01.2019
- URL: https://umo.abvpress.ru/jour/article/view/183
- DOI: https://doi.org/10.17650/2313-805X-2018-5-4-131-134
- ID: 183
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Abstract
Background. PRAME gene spontaneous expression is frequently observed in a cancer cell. The protein encoded by this gene increases the viability of tumour cell. NF-κB signalling pathway takes part in PRAME upregulation. It proposes, that stress conditions may increase the expression level of PRAME in the tumour cell and increase cell’s viability after it. We hypothesized that this phenomenon determines chemoresistance of PRAME-expressing cell, which can be overcome by NF-κB inhibitors, such as bortezomib.
Materials and methods. We incubated A875 melanoma cells with cisplatin, bortezomib and dexamethasone, as well as with a mixture of cisplatin with bortezomib and cisplatin with dexamethasone within 24 hours. To assess the cytotoxicity of these combinations MTT-test was used. For evaluation of PRAME expression level, real-time polymerase chain reaction was used. All data were analyzed with Wilcoxon test for coupled samples.
Results. It was found that cisplatin and dexamethasone increased an expression level of PRAME compared to control (p <0.03). The addition of dexamethasone to cisplatin reduced cytotoxic effect of cisplatin. Bortezomib has a cytotoxic effect, but it did not increase the activity of PRAME gene (p = 0.12). PRAME gene activity in cells incubated with a mixture of cisplatin and bortezomib was observed at a lower level in comparison with cells incubated with cisplatin (p = 0.0277).
Conclusion. The results of experiments show that an increase of PRAME expression level reduces the sensitivity of melanoma cells to the cytotoxic effect of cisplatin. PRAME activity increases under stress conditions. Using of bortezomib can inhibit the growth of PRAME expression and makes the tumour cell more vulnerable to cytotoxic agents. On the other hand, dexamethasone may increase a resistance of PRAME-expressing cell to cytotoxic effects.
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About the authors
V. A. Misyurin
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Author for correspondence.
Email: vsevolod.misyurin@gmail.com
ORCID iD: 0000-0002-0762-5631
24 Kashirskoe Shosse, Moscow 115478
Russian FederationD. V. Kalenichenko
K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology
Email: fake@neicon.ru
23 Akademika Skryabina St., Moscow 109472
Russian FederationA. A. Rudakova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Email: fake@neicon.ru
24 Kashirskoe Shosse, Moscow 115478
Russian FederationYu. P. Finashutina
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0002-6154-535X
24 Kashirskoe Shosse, Moscow 115478
Russian FederationN. A. Lyzhko
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0003-3834-5816
24 Kashirskoe Shosse, Moscow 115478
Russian FederationV. V. Tikhonova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0002-8658-2819
24 Kashirskoe Shosse, Moscow 115478
Russian FederationL. A. Kesaeva
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0001-8277-8649
24 Kashirskoe Shosse, Moscow 115478
Russian FederationO. N. Solopova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0002-5465-6094
24 Kashirskoe Shosse, Moscow 115478
Russian FederationA. Е. Misyurina
National Research Center for Hematology, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0002-9535-6688
4 Novyy Zykovskiy Proezd, Moscow 125167
Russian FederationA. N. Velikanov
M.V. Lomonosov Moscow State University
Email: fake@neicon.ru
ORCID iD: 0000-0002-3819-8564
1 Leninskie Gory, Moscow 119991
Russian FederationM. А. Baryshnikovа
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0002-6688-8423
24 Kashirskoe Shosse, Moscow 115478
Russian FederationA. V. Misyurin
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0003-1349-2879
24 Kashirskoe Shosse, Moscow 115478
Russian FederationReferences
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