Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/ijms23063183
Keywords
soft tissue sarcoma; chemosensitivity test; ABCB1; ABCC1; ABCG2; MVP; YB-1; Pgp; undifferentiated pleomorphic sarcoma; synovial sarcoma
Funding
- Russian Foundation of Basic Research [MK 18-29-09095]
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The aim of this study was to analyze the mechanism of multidrug resistance (MDR) in different types of soft tissue sarcomas (STS). The expression of ABC-transporters, MVP, and YB-1 were assessed, and their correlation with chemosensitivity of cancer cells was analyzed. Pgp expression was found in some STS samples and was strongly correlated with the sensitivity to certain chemotherapy drugs. Overall, STS demonstrated high heterogeneity in chemosensitivity, highlighting the importance of in vitro testing for personalized therapy.
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.
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