Analysis of Multiple Drug Resistance Mechanism in Different Types of Soft Tissue Sarcomas: Assessment of the Expression of ABC-Transporters, MVP, YB-1, and Analysis of Their Correlation with Chemosensitivity of Cancer Cells

Moiseeva, N.I.; Laletina, L.A.; Fetisov, T.I.; Makhmudova, L.F.; Manikaylo, A.E.; Fomina, L.Y.; Burov, D.A.; Lesovaya, E.A.; Bokhyan, B.Y.; Zinovieva, V.Y.; Vilkova, A.S.; Mekheda, L.V.; Kozlov, N.A.; Scherbakov, A.M.; Kirilin, E.M.; Belitsky, G.A.; Yakubovskaya, M.G.; Kirsanov, K.I.

Авторы: Moiseeva Natalia I., Laletina Lidia A., Fetisov Timur I., Makhmudova Leyla F., Manikaylo Angelika E., Fomina Liliya Y., Burov Denis A., Lesovaya Ekaterina A., Bokhyan Beniamin Yu, Zinovieva Victoria Y., Vilkova Alice S., Mekheda Larisa V., Kozlov Nikolay A., Scherbakov Alexander M., Kirilin Evgeny M., Belitsky Gennady A., Yakubovskaya Marianna G., Kirsanov Kirill I.
Журнал: International Journal of Molecular Sciences
Том: 23
Номер: 6
Год издания: 2022
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
DOI: 10.3390/ijms23063183
Аннотация: Chemotherapy of soft tissue sarcomas (STS) is restricted by low chemosensitivity and multiple drug resistance (MDR). The purpose of our study was the analysis of MDR mechanism in different types of STS. We assessed the expression of ABC-transporters, MVP, YB-1, and analyzed their correlation with chemosensitivity of cancer cells. STS specimens were obtained from 70 patients without metastatic disease (2018–2020). Expression level of MDR-associated genes was estimated by qRT-PCR and cytofluorimetry. Mutations in ABC-transporter genes were captured by exome sequencing. Chemosensitivity (SI) of STS to doxorubicin (Dox), ifosfamide (Ifo), gemcitabine (Gem), and docetaxel (Doc) was analyzed in vitro. We found strong correlation in ABCB1, ABCC1, and ABCG2 expression. We demonstrated strong negative correlations in ABCB1 and ABCG2 expression with SI (Doc) and SI (Doc + Gem), and positive correlation of MVP expression with SI (Doc) and SI (Doc + Gem) in undifferentiated pleomorphic sarcoma. Pgp expression was shown in 5 out of 44 STS samples with prevalence of synovial sarcoma relapses and it is strongly correlated with SI (Gem). Mutations in MDR-associated genes were rarely found. Overall, STS demonstrated high heterogeneity in chemosensitivity that makes reasonable in vitro chemosensitivity testing to improve personalized STS therapy, and classic ABC-transporters are not obviously involved in MDR appearance.
Добавил в систему: Фетисов Тимур Игоревич

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Analysis of Multiple Drug Resistance Mechanism in Different Types of Soft Tissue Sarcomas: Assessment of the Expression of ABC-Transporters, MVP, YB-1, and Analysis of Their Correlation with Chemosensitivity of Cancer Cellsстатья Исследовательская статья

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