Differential cytotoxicity of 19 anticancer agents in wild type and etoposide resistant small cell lung cancer cell lines

Pb, Jensen; Christensen, I. J.; Sehested, Maxwell; Hansen, H H; Vindeløv, Lars L.

doi:10.1038/bjc.1993.58

Cited by 30 publications

(23 citation statements)

References 36 publications

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Section: Clonogenic Assaymentioning

confidence: 52%

“…Similar data have been published previously (Chen et al, 1991;Hendriks et al, 1992). As expected from other studies, g concentration points in linear regression analysis on there is also cross-resistance to taxol and taxotere in this P-glycoically transformed response data (Jensen et al, 1993a).protein-positive cell line.concentrations chosen approximated to LD10, LD50 andIn Figure iB, NCI-H69 is compared with H69NVP cells which ined on cell line OC-NYH from dose-response curves in were selected for etoposide (VP-16) resistance. H69/VP exhibits Experiments and were as follows (,UM): BCNU (0.9, 2.3, the multidrug resistance protein (MRP) as well as P-glycoprotein and, in addition, immunohistochemistry demonstrates a clear cytoplasmatic localization of the etoposide target enzyme topo-lIIa (not shown).…”

mentioning

confidence: 99%

“…To obtain more dose-response curves on one batch of cells, we therefore developed an automatic colony counter (Jensen et al, 1993a). In each experiment, all 20 drugs (three concentrations of each, all plated in triplicate) and six control triplicates were tested on the same batch of cells.…”

Section: Clonogenic Assaymentioning

confidence: 99%

“…In contrast to these two extremes, i.e. the ultimate presence of a pan-resistant phenotype or the initial presence of a multidrugsensitive phenotype, we and others have found differential sensitivity patterns when investigating the cytotoxicity of various compounds in panels of cell lines (Schabel et al, 1983;Jensen et al, 1992Jensen et al, , 1993aWeinstein et al, 1992;Koutsoukos et al, 1994). Accordingly, one way of circumventing current drug resistance would be to develop new drug types that can act on cellular targets other than those already in use.…”

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confidence: 99%

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In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin

Jensen

Holm²,

Sørensen³

et al. 1997

Br J Cancer

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In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin PB Jensen1, B Holm', M Sorensen1, IJ Christensen2 and M Sehested3 'Laboratory of Experimental Medical Oncology, The Finsen Center, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark; 2The Finsen Laboratory, Rigshospitalet, DK-2100 Copenhagen; 3Department of Pathology, Righospitalet, DK-2100 Copenhagen Summary The acquisition of drug-resistant tumour cells is the main problem in the medical treatment of a range of malignant diseases. In recent years, three new classes of anti-cancer agents, each with a novel mechanism of action, have been brought forward to clinical trials. These are the topoisomerase (topo 1) poisons topotecan and irinotecan, which are both camptothecin derivatives, the taxane tubulin stabilizers taxol and taxotere and, finally, the antimetabolite gemcitabin, which is active in solid tumours. The process of optimizing their use in a combination with established agents is very complex, with numerous possible drug and schedule regimens. We describe here how a broad panel of drug-resistant small-cell lung cancer (SCLC) cell lines can be used as a model of tumour heterogeneity to aid in the selection of non-cross-resistant regimens. We have selected low-fold (3-1Ox) drug-resistant sublines from a classic (NCI-H69) and a variant (OC-NYH) SCLC cell line. The resistant cell lines include two sublines with different phenotypes towards alkylating agents (H69/BCNU and NYH/CIS), two sublines with different phenotypes against topo I poisons (NYH/CAM and NYH/TPT) and three multidrug resistant (MDR) sublines (H69/DAU, NYH/VM, and H69NP) with combinations of mdrl and MRP overexpression as well as topoisomerase 11 (topo 11) down-regulation or mutation. Sensitivity to 20 established and new agents was measured in a standardized clonogenic assay. Resistance was highly drug specific. Thus, none of the cell lines was resistant to all drugs. In fact, all resistant cell lines exhibited patterns of collateral sensitivity to various different classes of drugs. The most intriguing pattern was collateral sensitivity to gemcitabin in two cell lines and to ara-C in five drugresistant cell lines, i.e. in all lines except the lines resistant to topo poisons. Next, all sensitivity patterns in the nine cell lines were compared by correlation analysis. A high correlation coefficient (CC) for a given pair of compounds indicates a similar pattern in response in the set of cell lines. Such data corroborate the view that there is cross-resistance among the drugs. A numerically low coefficient indicates that the two drugs are acting in different ways, suggesting a lack of cross-resistance between the drugs, and a negative correlation coefficient implies that two drugs exhibit collateral sensitivity. The most negative CCs (%) to the new drug leads were: taxotere-carmustine (BCNU) (-75), taxol-cisplatin (-58), ara-C-taxol (-2...

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Section: Clonogenic Assaymentioning

confidence: 52%

mentioning

confidence: 99%

Section: Clonogenic Assaymentioning

confidence: 99%

mentioning

confidence: 99%

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In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin

Jensen

Holm²,

Sørensen³

et al. 1997

Br J Cancer

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“…Clonogenic assay was performed as described previously (Jensen et al, 1993). In brief, cells (passages 27 -35) were suspended in CM supplemented with penicillin (50 U/ml) and streptomycin (50 mg/ ml).…”

Section: Clonogenic Assaymentioning

confidence: 99%

TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis

et al. 2006

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Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of four inhibitors of the matrix metalloproteinases, which are capable of degrading most components of the extracellular matrix. However, in recent years, TIMP-1 has been recognised as a multifunctional protein, playing a complex role in cancer. In this regard, several studies have demonstrated an antiapoptotic effect of TIMP-1 in a number of different cell types. Since chemotherapy works by inducing apoptosis in cancer cells, we raised the hypothesis that TIMP-1 promotes resistance against chemotherapeutic drugs. In order to investigate this hypothesis, we have established TIMP-1 genedeficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene deficiency increases the response to chemotherapy considerably, confirming that TIMP-1 protects the cells from apoptosis. This is to our knowledge the first study investigating TIMP-1 and chemotherapy-induced apoptosis employing a powerful model system comprising TIMP-1 gene-deficient cells and their genetically identical wild-type controls. For future studies, this cell system can be used to uncover the mechanisms and signalling pathways involved in the TIMP-1-mediated inhibition of apoptosis as well as to investigate the possibility of using TIMP-1 inhibitors to optimise the effect of conventional chemotherapy.

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Single agent‐ and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

Michaelsen

Christensen

Sehested

et al. 2012

The Journal of Gene Medicine

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Differential cytotoxicity of 19 anticancer agents in wild type and etoposide resistant small cell lung cancer cell lines

Cited by 30 publications

References 36 publications

In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin

In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin

TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis

Single agent‐ and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

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