1.Histone deacetylase inhibitor MS-275 treatment alters immune molecule content and categories in hepatocarcinoma exosomes.
Qiu-wen LI ; Wen-hua XIAO ; Gaowa SARENGAOWA ; Wei-wei DONG ; Hui-xia ZHAO ; Xin-yu DUAN ; Jian-hua ZHU ; Huan-rong KANG ; Yan FU ; Yi-xin HAO ; Ru-liang WANG ; Lin-ping SONG ; Ming YE
Chinese Journal of Hepatology 2012;20(3):231-235
OBJECTIVETo investigate the effects of the histone deacetylase inhibitor, MS-275, on the immune molecule content and categories in hepatocarcinoma exosomes.
METHODSExosomes were isolated from the human hepatocarcinoma cell lines, HepG2 and Hep3b, and purified by a combination technique of ultrafiltration centrifugation and sucrose gradient ultracentrifugation. The expressions of heat shock protein (HSP)70, human leukocyte antigen (HLA)-I, HLA-DR, cluster of differentiation (CD) 80 and NY-ESO-1 on exosomes were analyzed with immunoelectron microscopy and Western blotting before and after MS-275 treatment. Intergroup differences were statistically analyzed by the Student's paired t-test.
RESULTSMS-275 treatment of both HepG2 and Hep3b cell types significantly increased the numbers of exosomes, their total protein content, and expression of HSP70, HLA-I and CD80 (per 100 exosomes), as compared to non-treated cells (all, P less than 0.01). MS-275 was also found to induce de novo expression of HLA-DR, but had no significant effect on NY-ESO-1 expression (P more than 0.05). The findings from immunoelectron microscopy confirmed those from Western blotting.
CONCLUSIONThe histone deacetylase inhibitor, MS-275, can significantly alter the immune molecule content and categories in exosomes of hepatocarcinoma cells. The differential expression profile may reflect an anti-cancer immune response and represent molecular targets for novel anti-hepatoma therapeutic or preventative strategies.
Antigens, Neoplasm ; immunology ; metabolism ; Benzamides ; pharmacology ; Carcinoma, Hepatocellular ; immunology ; metabolism ; Exosomes ; immunology ; metabolism ; Hep G2 Cells ; Histocompatibility Antigens Class I ; immunology ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Pyridines ; pharmacology
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