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        2,3,7,8-Tetrachlorodibenzo-P-Dioxin Induced Cell-Specific Drug Transporters With Acquired Cisplatin Resistance in Cisplatin Sensitive Cancer Cells

        Tuvshinjargal Gotovdorj,이은일,임용철,차은정,권대호,홍은영,김윤정,오민영 대한의학회 2014 Journal of Korean medical science Vol.29 No.9

        2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can induce drug transporter genes such as theATP-binding cassette G member 2 (ABCG2), which contributes to multidrug resistance. Weinvestigated the effect of TCDD pretreatment on drug transporters induction from cancercells of various origins. Cell viabilities after treatment of cisplatin were measured toevaluate acquiring cisplatin resistance by TCDD. Acquring cisplatin resistance was foundonly in cisplatin senstivie cancer cells including gastric SNU601, colon LS180, brain CRTMGand lymphoma Jurkat cells which showed a significant increase in cell viability aftercombined treatment with TCDD and cisplatin. High increase of ABCG2 gene expression wasfound in SNU601 and LS180 cells with a mild increase in the expression of the ABCC3,ABCC5,and SLC29A2 genes in SNU601 cells, and of major vault protein (MVP) in LS180cells. The AhR inhibitor kaempferol suppressed the upregulation of ABCG2 expression andreversed the TCDD-induced increase in cell viability in LS180 cells. However, in CRT-MGcells, other transporter genes including ABCC1, ABCC5, ABCA3, ABCA2, ABCB4, ABCG1,and SLC29A1 were up-regulated. These findings suggested the acquiring cisplatinresistance by TCDD associated with cancer cell-type-specific induction of drug transporters.

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