Lipids: Metabolism, Nutrition & Health

Biography

Biography: Chunfa Huang

Abstract

      Cholesterol       plays an important role in cancer de velopment,      drug resistance      and chemoi mmuno-sensitivity.      Statins     , cholesterol lowering drugs, can induce apoptosis, but also negatively interfere wit h CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo      immunotherapy      of chronic lymphocytic leukemia (CLL). We used MEC-2 cells, a CLL cell line, and the peripheral blood     mononuclear     cells (PBMCs) from    CLL    patients, treated them with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol le vels, CD-20 expression and distribution, a nd cell viability in the presence or absence of fludarabine,    rituximab    or their combinations. We found that MEC-2 cells treated with cholesterol lowering  agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular   cholesterol   levels, but also significantly promoted CD-20 surface expression. Furt hermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced   chemoimmuno-sensitivity   of the PBMCs from CLL patients. Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20  epitope  presentation or its downstream signaling. These results provide a n   ovel strategy which could be applied to CLL treatment.