ORIGINAL ARTICLE Differential effects of c-myc and ABCB1 silencing on reversing drug resistance in HepG2/Dox cells Shaymaa M. M. Yahya 1 & Ahmed R. Hamed 2 & Mohamed Emara 3 & Maha M. Soltan 2 & Gamal Eldein F. Abd-Ellatef 4 & Salma M. Abdelnasser 5 Received: 20 September 2015 /Accepted: 10 November 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015 Abstract Multidrug resistance (MDR) in various kinds of cancers represents a true obstacle which hinders the successes of most of current available chemotherapies. ATP-binding cassette (ABC) trasporter proteins have been shown to con- tribute to the majority of MDR in various types of malignan- cies. c-myc has recently been reported to participate, at least partly, in MDR to some types of cancers. This study aimed to test whether c-myc could play a role, solely or with coordina- tion with other ABCs, in the resistance of HepG2 cells to doxorubicin (Dox). MDR has been induced in wild-type HepG2 and has been verified both on gene and protein levels. Various assays including efflux assays as well as siRNA targeting ABCB1 and c-myc have been employed to explore the role of both candidate molecules in MDR in HepG2. Re- sults obtained, with regard to ABCB1 silencing on HepG2/ Dox cells, have shown that ABCB1-deficient cells exhibited a significant reduction in ABCC1 expression as compared to ABCB1-sufficient cells. However, these cells did not show a significant reduction in other tested ABCs (ABCC5 and ABCC10) while c-myc silencing had no significant effect on any of the studied ABCs. Moreover, silencing of ABCB1 on HepG2 significantly increased fluorescent calcein retention in HepG2 cells as compared to the control cells while downreg- ulation of c-myc did not have any effect on fluorescent calcein retention. Altogether, this work clearly demonstrates that c- myc has no role in MDR of HepG2 to Dox which has been shown to be ABCB1-mediated in a mechanism which might involve ABCC1. Keywords Multidrug resistance . HepG2/Dox . ABCB1 . ABCC1 . c-myc Introduction Cancer is the leading cause of death worldwide with hepato- cellular carcinoma (HCC) being one of the most common causes of cancer-related deaths worldwide. Resistance to che- motherapeutic agents is a major impedance to successful treat- ment of cancer. The increased expression of cell membrane transporters causes drug resistance which can increase efflux of the anticancer drugs from the cancer cells [1]. Therefore, understanding how chemoresistance develops and how it can be prevented is crucial for fighting cancer effectively. Multi- drug resistance (MDR) is a unique type of drug resistance wherein exposing the cells to a single chemotherapeutic agent is followed by cross resistance to a wide range of structurally and functionally unrelated drugs [2]. MDR is predominantly attributed to the overexpression of transmembrane drug efflux transporters in resistant cancer cells. These transporters are known as the ATP-binding cas- sette (ABC). ABC transporter represents the key component * Shaymaa M. M. Yahya yahshay10@yahoo.com 1 Hormones Department, Meical Division, National Research Centre, 33 El Bohouth st. (Former El Tahrir st.) Dokki, P.O. 12622 Giza, Egypt 2 Pharmaceutical Research Group, Center of Excellence for Advanced Sciences and Phytochemistry Department National Research Centre, 33 El Bohouth st. (Former El Tahrir st) Dokki, P.O. 12622 Giza, Egypt 3 Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Ein Helwan, P.O.X: 11795, Cairo, Egypt 4 Pharmaceutical and Drug Industries Research Division, Therapeutic Chemistry Department, National Research Center, 33 El Bohouth st. (Former El Tahrir st) Dokki, P.O. 12622, Giza, Egypt 5 Microbial Biotechnology Department, National Research Center, 33 El Bohouth st. (Former El Tahrir st) Dokki, P.O. 12622, Giza, Egypt Tumor Biol. DOI 10.1007/s13277-015-4426-7