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J Cell Mol Med ; 21(9): 1929-1943, 2017 09.
Article in English | MEDLINE | ID: mdl-28411377

ABSTRACT

MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR-495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR-495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol-doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre-treatment with miR-495 before chemotherapy could improve the curative effect on MDR1-based MDR cancer.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Doxorubicin/pharmacology , Drug Resistance, Multiple/genetics , Drug Resistance, Neoplasm/genetics , MicroRNAs/metabolism , Paclitaxel/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Animals , Base Sequence , Cell Line, Tumor , Down-Regulation/drug effects , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice, Inbred BALB C , MicroRNAs/genetics , RNA Interference , Rifampin/pharmacology
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