Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytokines
  • Disease Progression
  • Herpesvirus 8, Human
  • Humans
  • Mice
  • RNA, Messenger
  • Transcription, Genetic
  • Xenograft Model Antitumor Assays

MeSH Major

  • Autocrine Communication
  • Lymphoma
  • Sirolimus

abstract

  • The antitumor potency of the mTOR inhibitor rapamycin (sirolimus) is the subject of intense investigations. Primary effusion lymphoma (PEL) appears as an AIDS-defining lymphoma and like Kaposi sarcoma has been linked to Kaposi sarcoma-associated herpesvirus (KSHV). We find that (1) rapamycin is efficacious against PEL in culture and in a murine xenograft model; (2) mTOR, its activator Akt, and its target p70S6 kinase are phosphorylated in PEL; (3) rapamycin inhibits mTOR signaling as determined by S6 phosphorylation; (4) KSHV transcription is unaffected; (5) inhibition of IL-10 signaling correlates with drug sensitivity; and (6) addition of exogenous IL-10 or IL-6 can reverse the rapamycin growth arrest. This validates sirolimus as a new treatment option for PEL.

publication date

  • March 1, 2007

has subject area

  • Animals
  • Autocrine Communication
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytokines
  • Disease Progression
  • Herpesvirus 8, Human
  • Humans
  • Lymphoma
  • Mice
  • RNA, Messenger
  • Sirolimus
  • Transcription, Genetic
  • Xenograft Model Antitumor Assays

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1801055

Digital Object Identifier (DOI)

  • 10.1182/blood-2006-06-028092

PubMed ID

  • 17082322

Additional Document Info

start page

  • 2165

end page

  • 2173

volume

  • 109

number

  • 5