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

Authors:
Sang-Hoon Sin
Sang-Hoon Sin
Dept. Microbiology & Immunology / University of North Carolina at Chapel Hill
Research Assistant Professor
KSHV
Chapel Hill, NC | United States

Blood 2007 Mar 2;109(5):2165-73. Epub 2006 Nov 2.

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC 27599-7290, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2006-06-028092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1801055PMC
March 2007
8 Reads
10.452 Impact Factor

Publication Analysis

Top Keywords

lymphoma pel
8
primary effusion
8
effusion lymphoma
8
rapamycin efficacious
8
rapamycin
5
pel
5
pel culture
4
efficacious pel
4
addition exogenous
4
murine xenograft
4
culture murine
4
find rapamycin
4
xenograft model
4
model mtor
4
sensitivity addition
4
herpesvirus kshv
4
linked kaposi
4
sarcoma linked
4
transcription unaffected
4
il-10 il-6
4

Similar Publications