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

Karolina Wojtowicz1, Radoslaw Januchowski2, Michal Nowicki2

  • 1Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland k_wojtowicz@onet.pl.

Anticancer Research
|May 29, 2017
PubMed
Abstract

Insights

Vaults, particularly major vault protein (MVP) and vault poly-ADP-ribose polymerase (vPARP), are crucial for cancer drug resistance. Their depletion significantly reduces cancer cell viability and impacts multidrug resistance protein expression.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • The function of vault ribonucleoprotein particles remains complex.
  • Vaults are implicated in multidrug resistance (MDR) mechanisms.
  • This study investigates the role of vaults in cancer drug resistance.

Purpose of the Study:

  • To elucidate the specific roles of major vault protein (MVP) and vault poly-ADP-ribose polymerase (vPARP) in cancer cell drug resistance.
  • To explore the relationship between vault proteins and multidrug resistance proteins, such as P-glycoprotein (Pgp).

Main Methods:

  • Cell viability assessed using MTT assays.
  • Protein expression analyzed via western blot.
  • Gene silencing achieved through siRNA-mediated knockdown of MVP and vPARP.

Main Results:

  • Knockdown of MVP in W1PR cells led to a significant decrease in cell viability.
  • Knockdown of vPARP in multiple cell lines (LoVo/Dx, W1TR, A2780TR) also decreased cell viability.
  • MVP silencing in LoVo/Dx cells resulted in increased P-glycoprotein (Pgp) expression.

Conclusions:

  • Major vault protein (MVP) plays a significant role in cancer cell drug resistance.
  • Vault poly-ADP-ribose polymerase (vPARP) appears necessary for the full activation of MVP's role in drug resistance.
  • A functional correlation exists between vault proteins and MDR proteins, highlighting their cooperative roles.
Keywords:
BCRPVaultsbrefeldin Acastanosperminechemotherapyglycoprotein Pmultidrug resistancetunicamycin

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