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ctt-journal > Goreva et al. (Abstract)

Goreva et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 9
doi: 10.3205/ctt-2010-No9-abstract21
© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "4th Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation",
Saint Petersburg, Russia, September 18–20, 2010

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P-glycoprotein functional activity in healthy Caucasians and patients with non-Hodgkin’s lymphoma

Olga B. Goreva1, Elena V. Vorontsova1, Alevtina Y. Grishanova1, Oleg V. Mukhin2, Natalya P. Domnikova2, Vyacheslav V. Lyakhovich1

1Institute of Molecular Biology and Biophysics SD RAMS; 2Novosibirsk regional state clinical hospital, Novosibirsk, Russia

Correspondence: Olga B. Goreva, Institute of Molecular Biology and Biophysics SD RAMS, 2, Timakova str., 630017, Novosibirsk, Russia, E-mail: gorevao@spam is badgmail.com

Abstract

P-glycoprotein (P-gp) functions as a trans-membrane ATP-dependent pump, decreasing the intracellular concentration of different toxic substances, including antineoplastic agents. P-gp activity may influence the distribution and bioavailability of P-gp substrates, thereby changing the response to chemotherapy.

The aim of the investigation was to estimate the P-gp activity in a control group of healthy persons and patients with non-Hodgkin’s lymphoma (NHL), and analyze the relationship of P-gp function with tumor malignancy grade, chemotherapy protocols, and the response to chemotherapy.

Methods: P-gp activity was assessed using flow cytometric assay based on fluorescent

P-gp substrate rhodamine 123 (Rh123) efflux inhibition by P-gp inhibitor verapamil in lymphocytes in a control group of healthy persons (n=49) and patients with NHL (n=76).

Results: P-glycoprotein function in treated NHL patients was significantly (р=0.02) higher than in untreated patients. The study of P-gp function in NHL patients showed that P-gp activity was associated with a different tumor malignancy grade (p=0.01): P-gp activity in the patients with high-grade NHL was significantly (р=0.009) higher in comparison to patients with low-grade NHL. Although P-gp function in treated NHL patients tended to be higher in patients who received more aggressive chemotherapy, this difference wasn’t statistically significant. P-glycoprotein function was higher in chemoresistant patients (disease progression) than in those who were sensitive to chemotherapy (complete or partial remission, stable disease), but the difference did not reach a statistical significance.

In conclusion, P-gp activity was higher in patients with NHL than in the control group of healthy persons, and associated with tumor malignancy grade.

Keywords: P-glycoprotein activity, non-Hodgkin’s lymphoma, chemotherapy resistance

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