title: Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling.
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.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC 27599-7290, USA.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Sin
authors.forename: Debasmita
authors.initials: D
authors.lastname: Roy
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Staudt
authors.forename: Farnaz D
authors.initials: FD
authors.lastname: Fakhari
authors.forename: Dhavalkumar D
authors.initials: DD
authors.lastname: Patel
authors.forename: David
authors.initials: D
authors.lastname: Henry
authors.forename: William J
authors.initials: WJ
authors.lastname: Harrington
authors.forename: Blossom A
authors.initials: BA
authors.lastname: Damania
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D020123:Sirolimus