ABCMdb

PMID: 9740539

Etievant C, Barret JM, Kruczynski A, Perrin D, Hill BT
Vinflunine (20',20'-difluoro-3',4'-dihydrovinorelbine), a novel Vinca alkaloid, which participates in P-glycoprotein (Pgp)-mediated multidrug resistance in vivo and in vitro.
Invest New Drugs. 1998;16(1):3-17., [PubMed]

Sentences

No. Mutations Sentence Comment

79 ABCC1 p.Thr24Met ABCC1 p.Thr24Ser The T24 sensitive (T24S) parental and the resistant T24M subline [28] were obtained from Dr R. Kiss, Laboratory of Histology, Université Libre de Bel- gique, ULB (Brussels, Belgium). Login to comment 83 ABCC1 p.Thr24Met The less well-characterized T24M cells, selected for resistance to a cocktail of doxorubicin, NVB and DIAM 3 (an investigational alkylating compound [32]) has been described as expressing an increased level of Pgp [33]. Login to comment 87 ABCC1 p.Thr24Met ABCC1 p.Thr24Ser Cell culture conditions Parental and resistant human tumor cell lines were cultured in RPMI 1640 medium (Seromed, Poly- labo, Strasbourg, France) supplemented with 10% heat inactivated fetal calf serum (FCS, GIBCO, Cergy-Pontoise, France), except for T24S and T24M cells which were grown in MEM medium (GIBCO) supplemented with 5% FCS. Login to comment 92 ABCC1 p.Thr24Met Characteristics of the tumor resistant sublines studied in vitro and the culture conditions used Resistance phenotypea Tumor Selecting agent Seeding Resistance index Pgp MRP Topo II Cell line origin [maintenance density to selecting agent over- over- decreased concentration] [cells/ml] expression expression level P388/ADR [24,30] murine doxorubicin 4.0 × 104 66 + ± + leukemia [1 µM] CEM/VBL 1000 [25] human vinblastine 2.0 × 104 135 + nr - leukemia [1 µM] T24M [28,33] human DOX/NVB/DIAM3b 2.5 × 104 6/3600/50 + nr nr bladder ca.b [0.1/1/10 µg/ml] MCF7/200R [27,31] human doxorubicin 5.0 × 104 >222 + - + breast ca. Login to comment 185 ABCC1 p.Thr24Met The well-known Pgp-associated MDR sublines, CEM/VBL1000 and MCF7/200R and the less well-characterized T24M subline, all expressed definite cross-resistance to VFL, as they did to the three other tubulin-interacting agents tested. Login to comment 189 ABCC1 p.Thr24Met Furthermore, whilst the T24M cells showed a comparable high level of resistance to NVB (3600-fold) and to vincristine (3700- fold), these proved less cross resistant to vinblastine (1200-fold) and again were least resistant to VFL (840-fold). Login to comment 190 ABCC1 p.Thr24Met Overall, in this group of Pgp overexpressing human tumor cell lines, the T24M, and especially the MCF7/200R sublines proved consistently less cross-resistant to VFL compared with vinblastine, vin- Figure 4. Login to comment 198 ABCC1 p.Thr24Met Resistance indices for the different resistant cell lines Cell line Resistance Resistance indexa phenotype vinblastine vincristine vinorelbine vinflunine CEM/VBL1000 Pgp-MDR 135 1547 469 184 T24M Pgp-MDR 1200 3700 3600 840 MCF7/200R Pgp-MDR 684 2440 600 188 GLC4/ADR non Pgp-MDR 1 4 1 1 CEM/VM1 non Pgp-MDR 0.5 0.8 0.5 0.5 aResistance index = IC50 resistant cell line/IC50 sensitive cell line. Login to comment