期刊
MELANOMA RESEARCH
卷 27, 期 1, 页码 8-16出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CMR.0000000000000308
关键词
ABC transporters; apoptosis; aranoza; cancer-testis antigens; caspase-3; cisplatin; drug resistance; melanoma; streptozotocin; vasculogenic mimicry
资金
- Russian Scientific Foundation [14-35-00107]
The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug. Mel MeR cells were also cross-resistant to streptozotocin or cisplatin. Here, we show that aranoza-resistant melanoma cells modulate the ABC transporter activity, upregulate the expression of PRAME, adopt a vascular-related phenotype and engage in vasculogenic mimicry. LCS1269, a vasculogenic mimicry low-molecular-weight inhibitor, reverses the sensitivity of resistant melanoma cells to DNA-damaging agents. In this study, we provide experimental evidence that LCS1269 might be considered as a new potential anticancer agent capable of overcoming multidrug resistance for DNA-damaging agents in melanoma. Melanoma Res 27: 8-16 Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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