title: Differential effects of c-myc and ABCB1 silencing on reversing drug resistance in HepG2/Dox cells.
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 contribute to the majority of MDR in various types of malignancies. 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 coordination 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. Results 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 downregulation 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.
authors.affiliation: Hormones Department, Meical Division, National Research Centre, 33 El Bohouth st. (Former El Tahrir st.) Dokki, P.O. 12622, Giza, Egypt. yahshay10@yahoo.com.
authors.forename: Shaymaa M M
authors.initials: SM
authors.lastname: Yahya
authors.affiliation: 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.
authors.forename: Ahmed R
authors.initials: AR
authors.lastname: Hamed
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Ein Helwan, P.O.X: 11795, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Emara
authors.affiliation: 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.
authors.forename: Maha M
authors.initials: MM
authors.lastname: Soltan
authors.affiliation: 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.
authors.forename: Gamal Eldein F
authors.initials: GE
authors.lastname: Abd-Ellatef
authors.affiliation: Microbial Biotechnology Department, National Research Center, 33 El Bohouth st. (Former El Tahrir st) Dokki, P.O. 12622, Giza, Egypt.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Abdelnasser
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D016259:Genes, myc; D056945:Hep G2 Cells; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D004317:Doxorubicin
keywords: ABCB1; ABCC1; HepG2/Dox; Multidrug resistance; c-myc