Veliparib overcomes multidrug resistance in liver cancer cells

Biochem Biophys Res Commun. 2020 Jan 15;521(3):596-602. doi: 10.1016/j.bbrc.2019.10.141. Epub 2019 Oct 31.

Abstract

Overexpression of ATP-binding cassette (ABC) transporter is one of the most important factors taking responsibility for the progress of multidrug resistance (MDR) in multiple cancers. In this study, we investigated that veliparib, a PARP inhibitor which is in clinical development, could overcome ABCB1-mediated MDR in liver cancer cells. Veliparib could significantly enhance the cytotoxic effects of a series of conventional chemotherapeutic drugs in ABCB1-overexpression liver cancer cells. Mechanism study showed that veliparib could significantly enhance the accumulation of doxorubicin in ABCB1-overexpression liver cancer cells, without down-regulating the expression level of ABCB1. Finally, veliparib could significantly inhibit the ATPase activity of ABCB1 transporter. This study could provide information that combine veliparib with other chemotherapeutic drugs may benefit liver cancer patients.

Keywords: ABC transporter; Liver cancer; Multidrug resistance (MDR); Veliparib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Antineoplastic Agents / pharmacology*
  • Benzimidazoles / pharmacology*
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • Benzimidazoles
  • Poly(ADP-ribose) Polymerase Inhibitors
  • veliparib