Selective Drug Resistant Human Osteosarcoma Cell Lines

Cancer Treatment Reviews

2007

131

We undertook a systematic review of the pre-clinical and clinical literature for studies investigating the relationship between platinum and taxane resistance. Medline was searched for 1) cell models of acquired drug resistance reporting platinum and taxane sensitivities and 2) clinical trials of platinum or taxane salvage therapy in ovarian cancer.137 models of acquired drug resistance were identified. 68.1% of cisplatin-resistant cells were sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells were sensitive to cisplatin. A similar inverse pattern was observed for cisplatin vs docetaxel, carboplatin vs paclitaxel and carboplatin vs docetaxel. These associations were independent of cancer type, agents used to develop resistance and reported mechanisms of resistance. 65 eligible clinical trials of paclitaxel-based salvage after platinum therapy were identified. Studies of single agent paclitaxel in platinum-resistant ovarian cancer where patients had previously recieved paclitaxel had a pooled response rate of 35.3% n=232, compared to 22% in paclitaxel naïve patients n=1918 (p<0.01 Chi-squared). Suggesting that pretreatment with paclitaxel may improve the response of salvage paclitaxel therapy. The response rate to paclitaxel/platinum combination regimens in platinum-sensitive ovarian cancer was 79.5% n=88 compared to 49.4% n=85 for paclitaxel combined with other agents (p<0.001 Chi-squared), suggesting a positive interaction between taxanes and platinum. Therefore the inverse relationship between platinum and taxanes resistance seen in cell models is mirrored in the clinical response to these agents in ovarian cancer.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A systematic review of platinum and taxane resistance from bench to clinic: An inverse relationship

Stordal

Pavlakis

Cancer Treatment Reviews

2007

131

“…There are previous reports of cisplatin resistant SCLC cells being sensitised by pretreatment with a low dose of paclitaxel [28] and there are many examples of other cisplatin resistant cell lines that are sensitive to taxanes [48][49][50][51][52]. Taxanes bind to and stabilise microtubules and block cell cycle progression through centrosomal impairment, induction of abnormal spindles and suppression of spindle microtubule dynamics [53].…”

Section: Discussionmentioning

confidence: 99%

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Stordal

Cancer Chemother Pharmacol

2005

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines.Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models 3 of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC.

“…However, we know from work in resistant cell models developed with paclitaxel treatment that P-glycoprotein is associated with the inverse cisplatin/paclitaxel resistance phenotype. Resistant cell models developed using paclitaxel in nasal septum [54] , osteosarcoma [55] and ovarian cancer cells [3,56] have shown levels of paclitaxel resistance ranging from 8 to 1500-fold mediated by Pglycoprotein. There was no cross resistance to cisplatin in these cell models, many of which had become hypersensitive to cisplatin.…”

Section: Brca1 Mutationmentioning

confidence: 99%

A Systematic Review of Genes Involved in the Inverse Resistance Relationship Between Cisplatin and Paclitaxel Chemotherapy: Role of BRCA1

Stordal¹,

2009

CCDT

A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship between cisplatin and paclitaxel [1] . Here we systematically review genetically modified cell lines in which the inverse cisplatin/paclitaxel resistance phenotype has resulted. This will form a short list of genes which may play a role in the mechanism of the inverse resistance relationship as well as potential markers for monitoring the development of resistance in the clinical treatment of cancer. The literature search revealed 91 genetically modified cell lines which report toxicity or viability/apoptosis data for cisplatin and paclitaxel relative to their parental cell lines. This resulted in 26 genes being associated with the inverse cisplatin/paclitaxel phenotype. The gene with the highest number of genetically modified cell lines associated with the inverse resistance relationship was BRCA1 and this gene is discussed in detail with reference to chemotherapy response in cell lines and in the clinical treatment of breast, ovarian and lung cancer. Other genes associated with the inverse resistance phenotype included dihydrodiol dehydrogenase (DDH) and P-glycoprotein. Genes which caused cross resistance or cross sensitivity between cisplatin and paclitaxel were also examined, the majority of these genes were apoptosis associated genes which may be useful for predicting cross resistance. We propose that BRCA1 should be the first of a panel of cellular markers to predict the inverse cisplatin/paclitaxel resistance phenotype.3