P-glycoprotein activity in renal clear cell carcinoma

Soto-Vega, Elena; Arroyo, Carlos; Richaud-Patin, Yvonne; García-Carrasco, Mario; Vázquez-Lavista, Luis G.; Llorente, Luis

doi:10.1016/j.urolonc.2008.01.011

« Previous Next »Urologic Oncology: Seminars and Original Investigations
Volume 27, Issue 4 , Pages 363-366, July 2009

P-glycoprotein activity in renal clear cell carcinoma

Elena Soto-Vega, Ph.D.
- Unit of Research of Autoimmune Diseases, Instituto Mexicano del Seguro Social, Puebla, Mexico
- These authors collaborated equally to this work.
Carlos Arroyo, M.D., Ph.D.
- Department of Surgery, Hospital Universitario de Puebla, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
- These authors collaborated equally to this work.
Yvonne Richaud-Patin, B.S.
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico DF, Mexico
Mario García-Carrasco, M.D.
- Unit of Research of Autoimmune Diseases, Instituto Mexicano del Seguro Social, Puebla, Mexico
Luis G. Vázquez-Lavista, M.D.
- Department of Urology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico DF, Mexico
Luis Llorente, M.D.
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico DF, Mexico
- Corresponding author. Tel.: +(52) 55 56 55-5954; fax: +(52) 55 5517-2096

Received 22 November 2007; received in revised form 24 January 2008; accepted 25 January 2008. published online 28 April 2008.

Abstract

Background

The mechanism by which renal cancer patients show poor response to chemotherapy has not been well understood. The aim of this study was to evaluate the functional activity of P-glycoprotein (P-gp) in renal clear cell carcinoma (RCCC) and its possible role in chemotherapy resistance.

Methods

We studied 11 patients who underwent radical nephrectomy due to RCCC; from each patient we obtained a sample from the cancer tissue, and another from normal renal tissue. These biopsies were mechanically disaggregated to allow individual cells analysis. Cells were incubated with daunorubicin (a fluorescent drug extruded by P-gp) at 37°C and 4°C for 30 min. P-gp activity was analyzed using flow cytometry. Results were expressed as the percentage of cells with P-gp activity (i.e., low fluorescence).

Results

The analysis of renal cells showed that there was no significant difference in size between normal and cancer cells; however there were clusters of cells with different granularities. We divided the cells according to their granularity. The proportion of cells capable of extruding daunorubicin was significantly higher on tumor cells than in normal renal cells independently of the cell granularity. Our results are congruent with those obtained when mRNA or immunohistochemical test were used. This is the first report quantifying the P-gp activity from fresh samples obtained from kidney cancer in humans.