Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling
Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling
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DOI：
10.1182/blood-2006-06-028092
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发表时间：
2007-03-01
期刊：
影响因子：
20.3
通讯作者：
Dittmer, Dirk P.
中科院分区：
文献类型：
--
作者：
Sin, Sang-Hoon;Roy, Debasmita;Dittmer, Dirk P.
mTOR抑制剂雷帕霉素（西罗莫司）的抗肿瘤效力是深入研究的主题。原发性渗出性淋巴瘤（PEL）是一种艾滋病定义的淋巴瘤，与卡波西肉瘤一样，与卡波西肉瘤相关疱疹病毒（KSHV）有关。我们发现（1）雷帕霉素在培养物和鼠异种移植模型中对PEL有效;（2）mTOR、其激活剂Aid和其靶p70 S6激酶在PEL中被磷酸化;（3）雷帕霉素抑制mTOR信号传导，如通过S6磷酸化所确定的;（4）KSHV转录不受影响;（5）IL-10信号传导的抑制与药物敏感性相关;（6）外源性IL-10或IL-6的加入可以逆转雷帕霉素的生长停滞。这验证了西罗莫司作为PEL的新治疗选择。
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 Aid, 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.