Altered drug sensitivity in response to idarubicin treatment in K562 human leukaemia cells

Locke, Vicki L.; Davey, Ross A.; Davey, Mary W.

doi:10.1046/j.1365-2141.1999.01494.x

Cited by 10 publications

(5 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Colchicine, a P-gp substrate [33] selected for P-gp overexpression in KB-8-5-11 cells [34] and epirubicin, a MRP1 substrate [35] induced MRP1 expression in CCRF-CEM/E1000 [36]. However, methotrexate, fluorouracil, chlorambucil, cisplatin, and hydroxyurea have all been shown to transiently induce the expression of P-gp in K562 leukaemia cells when these drugs are not P-gp substrates [15].…”

Section: Discussionmentioning

confidence: 99%

Resistance to Paclitaxel in a Cisplatin-Resistant Ovarian Cancer Cell Line Is Mediated by P-Glycoprotein

et al. 2012

View full text Add to dashboard Cite

The IGROVCDDP cisplatin-resistant ovarian cancer cell line is also resistant to paclitaxel and models the resistance phenotype of relapsed ovarian cancer patients after first-line platinum/taxane chemotherapy. A TaqMan low-density array (TLDA) was used to characterise the expression of 380 genes associated with chemotherapy resistance in IGROVCDDP cells. Paclitaxel resistance in IGROVCDDP is mediated by gene and protein overexpression of P-glycoprotein and the protein is functionally active. Cisplatin resistance was not reversed by elacridar, confirming that cisplatin is not a P-glycoprotein substrate. Cisplatin resistance in IGROVCDDP is multifactorial and is mediated in part by the glutathione pathway and decreased accumulation of drug. Total cellular glutathione was not increased. However, the enzyme activity of GSR and GGT1 were up-regulated. The cellular localisation of copper transporter CTR1 changed from membrane associated in IGROV-1 to cytoplasmic in IGROVCDDP. This may mediate the previously reported accumulation defect. There was decreased expression of the sodium potassium pump (ATP1A), MRP1 and FBP which all have been previously associated with platinum accumulation defects in platinum-resistant cell lines. Cellular localisation of MRP1 was also altered in IGROVCDDP shifting basolaterally, compared to IGROV-1. BRCA1 was also up-regulated at the gene and protein level. The overexpression of P-glycoprotein in a resistant model developed with cisplatin is unusual. This demonstrates that P-glycoprotein can be up-regulated as a generalised stress response rather than as a specific response to a substrate. Mechanisms characterised in IGROVCDDP cells may be applicable to relapsed ovarian cancer patients treated with frontline platinum/taxane chemotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Resistance to Paclitaxel in a Cisplatin-Resistant Ovarian Cancer Cell Line Is Mediated by P-Glycoprotein

et al. 2012

View full text Add to dashboard Cite

show abstract

“…However, IGROVCDDP is a stably resistant cell line established by pulse selection using dose escalation (21). Pulse-selected cell lines which lose their resistant phenotype can also be maintained by re-treatment with the selecting dose (Figure 5C) such as K562/DNR resistant leukemia cells (17). Alternatively, instead of repeating the pulse treatment, resistant cells can be grown for a certain number of weeks or passages and then new stocks are defrosted of an earlier passage with the resistant phenotype present (Figure 5D).…”

Section: Maintaining Drug-resistant Cell Lines For Researchmentioning

confidence: 99%

In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies

et al. 2014

View full text Add to dashboard Cite

The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug resistance.

show abstract

“…This can be explained by the fact that resistance to daunorubicin and idarubicin is not completely mediated by alterations of the topo II enzymes (Zhou et al , 1999b). Furthermore, idarubicin‐resistant human K562 leukaemia cells were sensitive to VP (Locke et al , 1999).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological basis for cladribine resistance in a human acute T lymphoblastic leukaemia cell line selected for resistance to etoposide

et al. 2001

View full text Add to dashboard Cite

Summary. Cross-resistance between different classes of antineoplastic agents can jeopardize successful combination cancer chemotherapy. In this study, we observed an unexpected cross-resistance between the podophyllotoxine derivative etoposide (VP) and the nucleoside analogue cladribine (CdA) in CCRF-CEM cells developed for resistance to VP. The resistant cells also displayed 14-and twofold resistance to cytarabine (ara-C) and gemcitabine respectively. Closer analysis of these cells showed that they contained lower amounts of topoisomerase (topo) IIa (P , 0´001) and b protein (P , 0´026), formed substantially lower amounts of the topo II±DNA complex, and had a markedly decreased level of Fas (CD95/APO-1)-ligand mRNA expression. Interestingly, Fas expression in the resistant cells did not differ from that in the parental cell line. No differences were observed in the accumulation/ efflux of daunorubicin or in the gene expressions of Pglycoprotein, multidrug resistance-associated protein and the lung resistance-related protein. The activity of deoxycytidine kinase (dCK), responsible for activation of CdA and ara-C, was the same for resistant and wild-type cells. However, there was an increase in the activity of the cytosolic 5 0 -nucleotidases (5 0 -NT), responsible for deactivation of nucleotides, amounting to 206% (P , 0´001) for the high K m and 134% (P , 0´331) for the low K m 5 0 -NT in resistant cells. The high K m 5 0 -NT is probably responsible for the decreased amount of the active metabolite CdA 5 0 -triphosphate [40% decreased (P , 0´045)], as well as for other purine ribonucleosides and deoxyribonucleosides triphosphates in the resistant cells. In contrast, a significantly higher deoxycytidine triphosphate (dCTP) level (167%, P , 0´001) was observed in the resistant cells. Thus, this study suggests that the major cause of resistance to the nucleoside analogues CdA and ara-C in cells selected for resistance to VP is a result of metabolic alterations producing increased activity of 5 0 -NT and higher dCTP levels. Furthermore, these results indicate that there is a common factor in the regulation of nucleotide-degrading enzymes and DNA topoisomerases, which may be altered in cross-resistant cells.

show abstract

Altered drug sensitivity in response to idarubicin treatment in K562 human leukaemia cells

Cited by 10 publications

References 17 publications

Resistance to Paclitaxel in a Cisplatin-Resistant Ovarian Cancer Cell Line Is Mediated by P-Glycoprotein

Resistance to Paclitaxel in a Cisplatin-Resistant Ovarian Cancer Cell Line Is Mediated by P-Glycoprotein

In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies

Pharmacological basis for cladribine resistance in a human acute T lymphoblastic leukaemia cell line selected for resistance to etoposide

Contact Info

Product

Resources

About