Tumor Biology

, Volume 37, Issue 5, pp 5925–5932 | Cite as

Differential effects of c-myc and ABCB1 silencing on reversing drug resistance in HepG2/Dox cells

  • Shaymaa M. M. Yahya
  • Ahmed R. Hamed
  • Mohamed Emara
  • Maha M. Soltan
  • Gamal Eldein F. Abd-Ellatef
  • Salma M. Abdelnasser
Original Article

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.

Keywords

Multidrug resistance HepG2/Dox ABCB1 ABCC1 c-myc 

Notes

Acknowledgments

This work was supported by grants from the Science and Technology Development Fund (STDF), Egypt, Basic and Applied Research Grant (Project ID 4361). We thank Ghada H. El-sayed, Heba K. Nabih, Eman M. Abdel Motaleb, and Alaa Shahin for technical help.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • 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
  1. 1.Hormones Department, Meical DivisionNational Research CentreGizaEgypt
  2. 2.Pharmaceutical Research Group, Center of Excellence for Advanced Sciences and Phytochemistry Department National Research CentreGizaEgypt
  3. 3.Department of Microbiology and Immunology, Faculty of PharmacyHelwan UniversityCairoEgypt
  4. 4.Pharmaceutical and Drug Industries Research Division, Therapeutic Chemistry DepartmentNational Research CenterGizaEgypt
  5. 5.Microbial Biotechnology DepartmentNational Research CenterGizaEgypt

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