Reactive oxygen species promote doxorubicin-induced P-gp expression in colon cancer cells

JOINT EVENT:19^th Euro Congress on Cancer Science and Therapy & 25^th Cancer Nursing & Nurse Practitioners Conference

July 17-19, 2017 Lisbon, Portugal

Martha L Pinzon-Daza, Yenith Cuellar-Saenz, Francisco Nualart, Alejandro OndoMendez, Fabio Castillo-Rivera, Lilia Del Riesgo and Ruth Garzon

Universidad del Rosario, Colombia
Universidad Nacional de Colombia, Colombia
Universidad de Concepci�³n, Chile

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

Multidrug resistance (MDR) could be one of the most important problems associated to chemotherapy. P-glycoprotein (P-gp) and BCRP (breast cancer resistant protein) are ABC transporters that could be expressed in different cancer cell lines resistant to various drugs used for the treatment of cancer. Many of the anti-tumor chemotherapeutics like doxorubicin, induces reactive oxygen species (ROS) at a high level. In this study we investigated if doxorubicin-induced ROS generation could be involved on P-gp and BCRP expression promoting MDR in colon cancer cells. We analyzed ROS accumulation, Pgp and BCRP expression by qPCR and the relationship between doxorubicin uptake and ABC transporters expression by confocal microscopy using HT-29 WT and HT- 29 Doxorubicin-resistant colon cancer cells (HT-29Doxo) treated with doxorubicin. We used N-acetyl cysteine (NAC) as a control of ROS and APE-1 endonuclease inhibitor E-3330 as a modulator of oxidative stress activity. We showed that doxorubicin-induced ROS generation occurs in a time-dependent manner. Increasing ROS accumulation induced a slowly increased Pgp expression in HT29-WT treated whit doxorubicin and NAC similar to cells treated whit doxorubicin alone. In contrast BCRP expression had a significant reduction whit doxorubicin use and NAC. Furthermore APE-1 inhibitor E3330 induced Pgp and BCRP downregulation and at the same time an increased on doxorubicin accumulation higher than cells no treated. Our results suggest that MDR could be modulated by a mechanism associated to oxidative stress produce by use of doxorubicin in colon cancer cells. Additionally disrupting ROS accumulation could favor cancer therapy.

Biography :

Email: martha.pinzon@urosario.edu.co