Abstract
Aim:
To reverse the multidrug resistance (MDR) by RNA interference (RNAi)-mediated MDR1 suppression in hepatoma cells.
Methods:
For reversing MDR by RNAi technology, two different short hairpin RNAs (shRNAs) were designed and constructed into pGenSil-1 plasmid, respectively. They were then transfected into a highly adriamycin-resistant HepG2 hepatoma cell line (HepG2/ADM). The RNAi effect on MDR was evaluated by real-time PCR, cell cytotoxicity assay and rhodamine 123 (Rh123) efflux assy.
Results:
The stably-transfected clones showed various degrees of reversal of MDR phenotype. Surprisingly, the MDR phenotype was completely reversed in two transfected clones.
Conclusion:
MDR can be reversed by the shRNA-mediated MDRI suppression in HepG2/ADM cells, which provides a valuable clue to make multidrug-resistant hepatoma cells sensitive to anti-cancer drugs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
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Antibiotics, Antineoplastic / therapeutic use
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Carcinoma, Hepatocellular / drug therapy
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Carcinoma, Hepatocellular / genetics*
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Cell Line, Tumor
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Doxorubicin / therapeutic use
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Drug Resistance, Multiple / genetics*
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Drug Resistance, Multiple / physiology*
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Drug Resistance, Neoplasm / genetics
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Drug Resistance, Neoplasm / physiology
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Gene Expression Regulation, Neoplastic
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Genes, MDR / genetics*
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Humans
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Liver Neoplasms / drug therapy
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Liver Neoplasms / genetics*
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Phenotype
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RNA / pharmacology
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RNA Interference / physiology*
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Suppression, Genetic / drug effects
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Suppression, Genetic / genetics*
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Transfection
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antibiotics, Antineoplastic
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RNA, Messenger
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RNA, Small Interfering
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RNA
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Doxorubicin