[Treosulfan displays cytotoxic effect on spheroids of primary cell cultures of renal cell carcinoma independent of p-glycoprotein expression].
Therapy of advanced renal cell carcinoma remains difficult. New therapeutic schemes besides cytokine treatment should be evaluated. The following study analyzes the in vitro toxicity of treosulfan on spheroids of 8 primary cultures of renal cell carcinoma cells. these data were compared to the toxicity of vinblastine. All investigations were performed in regard to the P-glycoprotein (Pgp) expression of the cells, which is one of the main causes of multidrug resistance. Four Pgp positive and four Pgp negative spheroids were incubated with the drugs in increasing doses. Toxicity was measured using the MTT toxicity assay as well as trypan blue exclusion. Significantly higher toxicity of treosulfan compared to vinblastine could be demonstrated. In addition, the effects of treosulfan were not related to Pgp expression. These results are encouraging and a phase II study analyzing the efficacy of treosulfan in patients with advanced renal cell carcinoma has been initiated in our institution.
Kugler
A
A
Abteilung Urologie, Georg-August-Universität Göttingen.
Hemmerlein
B
B
Gross
A J
AJ
Seseke
F
F
Kallerhoff
M
M
Ringert
R H
RH
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002066:Busulfan / Q000031:analogs & derivatives* / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008856:Microscopy, Fluorescence; D018874:Spheroids, Cellular / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology
D018906:Antineoplastic Agents, Alkylating; D014747:Vinblastine; C018404:treosulfan; D002066:Busulfan