Submitted June 15, 2006
Accepted October 5, 2006
Rapamycin is efficacious against primary effusion
lymphoma (PEL) cell lines in vivo by inhibiting
autocrine signaling
Sang-Hoon Sin, Debasmita Roy, Ling Wang, Michelle R Staudt, Farnaz D Fakhari, Dhavalkumar D Patel, David Henry, William J Harrington, Blossom A Damania, and Dirk P Dittmer*
University of North Carolina at Chapel Hill
University of Pennsylvania
University of Miami
* Corresponding author; email: ddittmer{at}med.unc.edu.
The anti tumor potency of the mTOR inhibitor rapamycin (sirolimus) is the subject of intense investigations. Primary effusion lymphoma (PEL) appears concomitant with Kaposi's sarcoma as an AIDS and Kaposi's sarcoma-associated herpesvirus (KSHV) linked neoplasm. We find that (i) rapamycin is efficacious against PEL in culture and in a murine xenograft model; (ii) mTOR, it's activator Akt and its target p70S6 kinase are phosphorylated in PEL; (iii) rapamycin inhibits mTOR signaling as determined by S6 phosphorylation; (iv) KSHV transcription is unaffected; (v) inhibition of IL-10 signaling correlates with drug sensitivity; and (vi) addition of exogenous IL-10 or IL-6 can reverse the rapamycin growth arrest. This validates sirolimus as a new treatment option for PEL.
