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01-04-2010 | Original Article

Celecoxib inhibits MDR1 expression through COX-2-dependent mechanism in human hepatocellular carcinoma (HepG2) cell line

Authors: Karnati R. Roy, Gorla V. Reddy, Leela Maitreyi, Smita Agarwal, Chandrani Achari, Shireen Vali, Pallu Reddanna

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2010

Abstract

The role of COX-2 in the regulation of the expression of MDR1, a P-glycoprotein involved in hepatocellular carcinoma cell line, HepG2, was studied in the present investigation. Celecoxib, a selective inhibitor of COX-2, at 25 μM concentration increased the accumulation of doxorubicin in HepG2 cells and enhanced the sensitivity of the cells to doxorubicin by tenfold. The induction of MDR1 expression by PGE₂ and its downregulation by celecoxib or by COX-2 knockdown suggests that the enhanced sensitivity of HepG2 cells to doxorubicin by celecoxib is mediated by the downregulation of MDR1 expression, through COX-2-dependent mechanism. Further studies revealed the involvement of AP-1 in the celecoxib-induced downregulation of MDR1 expression. These experimental studies correlated well with in silico predictions and further suggested the inactivation of the signal transduction pathways involving ERK, JNK and p38. The present study thus demonstrates the usefulness of COX-2 intervention in overcoming the drug resistance in HepG2 cells.

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Title: Celecoxib inhibits MDR1 expression through COX-2-dependent mechanism in human hepatocellular carcinoma (HepG2) cell line
Authors: Karnati R. Roy
Gorla V. Reddy
Leela Maitreyi
Smita Agarwal
Chandrani Achari
Shireen Vali
Pallu Reddanna
Publication date: 01-04-2010
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-1097-3

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