Expression of SLC transporters in Chronic Lymphocytic Leukaemia cells and their interaction with cytostatics

Expression of SLC transporters in Chronic Lymphocytic Leukaemia cells and their interaction with cytostatics

Shivangi Gupta

Doctoral thesis

Date of Examination: 2009-10-12

Date of issue: 2009-11-18

Advisor: Pieler, Tomas Prof. Dr.

Referee: Groß, Uwe Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-000D-F172-3

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Abstract

English

Chronic Lymphocytic Leukaemia, CLL, is one of the most common forms of leukaemia in the elderly. The treatment regimen determines the outcome of patients with CLL and the efficiency of this treatment is modulated by the concentration of cancer treating drugs in cancer cells. Uptake transporters of the SLC (solute carrier) family can help overcome chemoresistance by the application of transporter-specific cytostatics. In the present study, we investigated the expression of SLC transporters in six lymphoma cell lines and in CLL patient samples. Five of the six cell lines tested, as well as samples from CLL patients demonstrated a higher expression of SLC22A1 (OCT1) than in healthy lymphocytes. The uptake of the organic cation [3H]MPP into OCT1 stably transfected CHO cells was significantly inhibited by irinotecan, mitoxantrone and paclitaxel. The Ki values as determined using Dixon plot analyses were 1.71

Keywords: SLC transporters; CLL; OCT1; Irinotecan; Paclitaxel

Schlagwörter: SLC transporters; CLL; OCT1; Irinotekan; Paclitaxel