HIV protease inhibitor Lopinavir induces apoptosis of primary effusion lymphoma cells via suppression of NF-κB pathway

Cancer Lett. 2014 Jan 1;342(1):52-9. doi: 10.1016/j.canlet.2013.08.045. Epub 2013 Sep 5.

Abstract

Primary effusion lymphoma (PEL) is a non-Hodgkin lymphoma that occurs predominantly in patients with advanced AIDS. In this study, we examined the effect of HIV protease inhibitors, Lopinavir (LPV), Ritonavir (RTV) and Darunavir (DRV) on PEL cell lines in vitro and in vivo. LPV and RTV, but not DRV induced caspase-dependent apoptosis and suppressed NF-κB activity by inhibiting IKK phosphorylation in PEL cells. In a PEL xenograft mouse model, LPV significantly inhibited the growth and invasion of PEL cells. These results suggest that LPV may have promise for the treatment and prevention of PEL, which occurs in HIV/AIDS patients.

Keywords: HIV-1 protease inhibiton; IκB kinase; NF-κB; Primary effusion lymphoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • HIV Protease Inhibitors / pharmacology*
  • HIV Protease Inhibitors / therapeutic use
  • Herpesvirus 8, Human / drug effects
  • Herpesvirus 8, Human / physiology
  • Humans
  • Lopinavir / pharmacology*
  • Lopinavir / therapeutic use
  • Lymphoma, Primary Effusion / drug therapy*
  • Lymphoma, Primary Effusion / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • NF-kappa B / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Tumor Burden / drug effects
  • Virus Activation / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • HIV Protease Inhibitors
  • NF-kappa B
  • Lopinavir
  • Proto-Oncogene Proteins c-akt