Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling.
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.
Sin
Sang-Hoon
SH
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC 27599-7290, USA.
Roy
Debasmita
D
Wang
Ling
L
Staudt
Michelle R
MR
Fakhari
Farnaz D
FD
Patel
Dhavalkumar D
DD
Henry
David
D
Harrington
William J
WJ
Damania
Blossom A
BA
Dittmer
Dirk P
DP
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
D016207:Cytokines; D012333:RNA, Messenger; D020123:Sirolimus