Characterization of Vincristine-Resistant HOB1 Lymphoma Cell Line Showing the Classical MDR Phenotype and Altered Expression of Membrane Glycoproteins

Abstract

A multidrug-resistant (MDR) cell line isolated from HOB1 lymphoma cells was characterized. The MDR phenotype in this cell line was typified by resistance to vincristine with varying degrees of cross-resistance to Adriamycin, colcemid and actinomycin D. Decreased intracellular [³H]vincristine with concurrent increase in the expression of a 170-kDa membrane glycoprotein (P-glycoprotein) suggested a plausible underlying mechanism for the development of resistance. Amplification of the mdr1gene as well as a homogeneous staining region on the long arm of the 7th chromosome was observed. Moreover, metabolic studies with [¹⁴C]glucosamine or [¹⁴C]mannose indicated differential expressions of membrane glycoproteins between the drug-sensitive parental and drug-resistant descendant cells. It is concluded that the development of drug resistance in HOB1 lymphoma cells was strongly correlated with the overexpression of P-glycoprotein.

Molecular cytogenetic characterization of doxorubicin‐resistant neuroblastoma cell lines: Evidence that acquired multidrug resistance results from a unique large amplification of the 7q21 region

“…However, expression of MDR1 was dramatically increased in both resistant sublines, as measured by real‐time PCR and Western blotting. Increased expression of MDR1 in association with in vitro–acquired chemoresistance in cell lines is common (Slovak et al, 1987; Lee and Lee, 1994; Zhou et al, 1996; Struski et al, 2002; Thomas and Coley, 2003; Longley and Johnston, 2005). However, in IGRN‐91R and LAN‐1R cells, it was clear that P‐gp‐mediated efflux as the sole contributor to the MDR phenotype was unlikely and that other, as‐yet‐unidentified mechanisms were involved.…”

“…These findings support overexpression of the MDR1 gene product, P‐gp, which was measured at mRNA and protein levels. Rearrangements involving the 7q21 region, such as amplifications, translocations, or duplications, have frequently been observed in drug‐resistant tumors and cell lines (Slovak et al, 1987; Lee and Lee, 1994; Zhou et al, 1996; Mickley et al, 1997; Struski et al, 2002; Thomas and Coley, 2003; Longley and Johnston, 2005). In a majority of cases, the genomic alterations involving the MDR1 locus were accompanied by several other genomic rearrangements.…”

Método para la obtención de una línea celular tumoral resistente a vincristina

“…El punto de máxima sensibilidad celular es durante la metafase, teniendo como principales efectos la dispersión y desorganización del material cromosómico, que desencadenará finalmente la muerte celular. La resistencia a estos fármacos puede deberse tanto a su baja capacidad para ingresar a la célula debido a la sobre-expresión de la gp-P, como a la disminución en su capacidad de fijación a tubulina debido a alteraciones en sus subunidades sin embargo, este último mecanismo de resistencia puede contrarrestarse empleando taxanos, que inhiben la desagregación de los microtúbulos, ya que los sitios de acción de los alcaloides de la vinca son distintos a los de los taxanos y la colchicina [7][8][9][10][11][12][13][14][15][16].…”