アクティブボード・２０１５年１２月
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研究発表を行った学会；
・第77回日本血液学会学術集会
　２０１５年１０月１６日〜１８日（金沢市）
タイトル；Chloroquine inhibits autophagy and induces the apoptosis of primary effusion lymphoma via ER stress.
発表者；Masud Alam　氏
　　　（熊本大学　エイズ学研究センター　岡田プロジェクト研究室）
要旨；
Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin B cell lymphomas that occurred predominantly in patients with advanced AIDS. Chloroquine is an anti-malarial drug but unclear in the treatment of hematological malignancies. Therefore, we examined the effect of chloroquine on PEL cells in vitro and in vivo. AnnexinV assay revealed that PEL cells were efficaciously killed by chloroquine in vitro. Chloroquine was found to inhibit autophagolysosome formation by increasing the accumulation of LC3-II protein on autophagosome. Chloroquine stimulated the agglomeration of unfolded protein within aggresomes that induced endoplasmic reticulum (ER) stress mediated caspase dependent apoptosis in PEL. Chloroquine induced CHOP, an ER stress marker and induction of cleaved caspase 3, an apoptotic marker in PEL. Additionally, caspase 3 and ER stress inhibitor rescued PEL cells from chloroquine induced apoptosis. In a PEL xenograft mouse model, GTO cells were intraperitoneally inoculated into Nude-Rag2/Jak3 double deficient mice, and treated with chloroquine or PBS once a day for 21 days. Chloroquine reduced the amount of ascites without significant systemic toxicity in mice model. These results suggest that chloroquine has given a promising reagent for the treatment and prevention of PEL in the HIV/AIDS patients.