vPARP Adjusts MVP Expression in Drug-resistant Cell Lines in Conjunction with MDR Proteins

Anticancer Res. 2017 Jun;37(6):3015-3023. doi: 10.21873/anticanres.11656.

Abstract

Background/aim: The definition of vault (ribonucleoprotein particles) function remains highly complex. Vaults may cooperate with multidrug resistance (MDR) proteins, supporting their role in drug resistance. This topic is the main theme of this publication.

Materials and methods: The cell viability was determined by an MTT assay. The protein expression was detected by western blot analysis. The proteins were knocked-down using siRNA.

Results: No major vault protein (MVP) in the LoVo/Dx and W1PR cell lines after tunicamycin treatment was shown. In W1PR cells with knocked-down MVP, a statistically significant decrease in cell viability was noted. In LoVo/Dx, W1TR and A2780TR cells were vault poly-ADP-ribose polymerase (vPARP) was knockdown, a decrease in cell viability was shown. Also, MVP silencing induced an increase in glycoprotein P (Pgp) expression in LoVo/Dx cells.

Conclusion: MVP is important for the drug resistance of cancer cells, but it probably requires the presence of vPARP for full activation. Some correlations between MDR proteins and vaults exist.

Keywords: BCRP; Vaults; brefeldin A; castanospermine; chemotherapy; glycoprotein P; multidrug resistance; tunicamycin.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism*
  • Antineoplastic Agents / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Resistance, Multiple / physiology*
  • Drug Resistance, Neoplasm / physiology*
  • Gene Silencing
  • Humans
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*
  • RNA-Binding Proteins
  • Vault Ribonucleoprotein Particles / genetics
  • Vault Ribonucleoprotein Particles / metabolism*

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • Carrier Proteins
  • RNA-Binding Proteins
  • TEP1 protein, human
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • Poly(ADP-ribose) Polymerases
  • vault poly(ADP-ribose) polymerase