Abstract
S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / antagonists & inhibitors
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ATP-Binding Cassette Transporters / metabolism*
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Adenosine / analogs & derivatives
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Adenosine / pharmacology
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Animals
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Antineoplastic Agents / pharmacology
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Cell Cycle
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Cell Line, Tumor
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Cell Proliferation
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Cell Survival / drug effects
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Cisplatin / pharmacology
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Colonic Neoplasms* / metabolism
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Colonic Neoplasms* / pathology
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Diketopiperazines
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Doxorubicin / metabolism
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Drug Resistance, Multiple*
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Drug Resistance, Neoplasm*
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Female
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Heterocyclic Compounds, 4 or More Rings
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Humans
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Inhibitory Concentration 50
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KB Cells
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Mitoxantrone / pharmacology
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / metabolism*
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Neoplasm Transplantation
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Rhodamine 123 / metabolism
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Topotecan / pharmacology
Substances
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3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl ester
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Antineoplastic Agents
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Diketopiperazines
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Heterocyclic Compounds, 4 or More Rings
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Neoplasm Proteins
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Rhodamine 123
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Topotecan
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Doxorubicin
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Mitoxantrone
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Adenosine
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Cisplatin