title: Combination of YM155, a survivin suppressant with a STAT3 inhibitor: a new strategy to treat diffuse large B-cell lymphoma.
abstract: Survivin and STAT3 pathway have been reported to be important for the growth of diffuse large B-cell lymphoma (DLBCL) cells. Here we investigated the antitumor activity of sepantronium bromide (YM155), a survivin suppressant, in combination with STAT3 inhibitors in DLBCL cell lines in vitro. YM155 synergistically enhanced STAT3 inhibitors (AG490 and STA-21)-induced apoptosis in DLBCL cell lines. Moreover, rituximab, which shows inhibitory activity against STAT3, also sensitized DLBCL cell lines to YM155 regardless of sensitivity to rituximab. These results suggest that combining the inhibition of survivin with STAT3 pathway is an attractive and potentially effective way for the treatment of DLBCL.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki, Japan. naoki.kaneko@astellas.com
authors.forename: Naoki
authors.initials: N
authors.lastname: Kaneko
authors.forename: Aya
authors.initials: A
authors.lastname: Kita
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Masamichi
authors.initials: M
authors.lastname: Mori
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009285:Naphthoquinones / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077022:Survivin; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D011083:Polycyclic Compounds; C500947:STA-21; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C523798:sepantronium
keywords: DLBCL; Rituximab; STAT3; Survivin; YM155