アクティブボード・２０１７年１月
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研究発表を行った学会；
・The 5th JCA-AACR Special Joint Conference
　　2016年7月13日〜15日（舞浜、千葉）

タイトル；Inhibitory Effect on Lymphoma Cells Proliferation by Regulating Cholesterol Metabolism Pathway.
発表者；藤原　章雄　氏
　　　（熊本大学　大学院生命科学研究部　細胞病理学分野）
要旨；
Cholesterol is one of main component composed of cell wall membrane, and also known as a substrate of bile acid and steroidogenic hormones. Free and esterified cholesterol is containing in chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) in blood stream, and LDL is known to be prominent carrier of cholesterol in blood. As cancer cells grow and proliferate, cholesterol has to be up-taken in cancer cells and cholesterol metabolism is up-regulated in cancer cells. Since free cholesterol is harmful to cells via unknown mechanisms, free cholesterol has to be quickly esterified by ACAT. Based on this mechanism, many researchers tried to treat the cancer cells by ACAT inhibitor, however, limited anti-cancer effect of ACAT inhibitors was observed. Although the reasons of this limited anti-cancer effect has been uncovered, we suggested that blocking the cholesterol efflux showed more effective for anti-cancer therapy. SR-BI is expressed on cell surface membrane of many cells including cancer cells, and involved in cholesterol efflux via HDL. Therefore we suggest the SR-B1 as a novel target for anti-cancer therapy.
It is well known that many vacuoles are detected in cytoplasm in Burkkit lymphoma cells, and this vacuole is one of important finding for the morphological diagnosis. Interestingly, we newly noticed that this “vacuole” is often observed in high grade B-cell and T-cell lymphoma, and esterified cholesterol is a main component of this “vacuole”. In our unpublished data, SR-BI was found to be overexpressed on lymphoma cell lines. High grade lymphoma cell might be more sensitive to inhibition of cholesterol metabolism. Based on these background, we hypothesized SR-BI inhibitor and ACAT inhibitor are effective to high grade lymphoma cells in which cholesterol metabolism is up-regulated.
In the present study, we revealed that SR-BI inhibitor significantly inhibited lymphoma cell proliferation and ACAT inhibitor also inhibited lymphoma cell proliferation. Furthermore, synergistic effect of SR-BI inhibitor and ACAT inhibitor was observed in in vitro study and the administration of SR-BI inhibitor suppressed lymphoma progression in tumor-bearing mice model. Therefore, those data indicates that the application of SR-BI inhibitors and ACAT inhibitors is a potential new anti-lympoma therapy targeting cholesterol metabolism pathway in lymphoma.