Figure 6.
Figure 6. OBN counteracts microenvironment-dependent drug resistance in MCL cells. (A) Maver-1 cocultured or not on L-40L cells, and Z138 and JeKo-1 cell lines were treated with VNT for 48 hours at the indicated doses with or without OBN pretreatment (0.5 µg/mL). *Observed value > expected value. (B) Maver-1 cells, in the presence of an L-40L coculture layer, were cultured with OBN (24 hours, 5 µg/mL) alone or in sequential combination with OBN (24 hours, 5 µg/mL) and then VNT (48 hours, 50 nM), cytarabine (AraC; 48 hours, 80 ng/mL) or BDM (48 hours, 100 µM). (C) OBN (48 hours; 0.5 µg/mL) but not RTX (48 hours; 0.5 µg/mL) induced direct cell death in reactivated primary MCL cells (7 days on L-40L+Ck; n = 4); paired Student t test. (D) OBN (48 hours; 0.5 µg/mL) induced direct cell death in L-40L+Ck cocultured primary MCL cells (7 days on L-40L+Ck; n = 12) but not in MCL cell lines (n = 4); Student t test. (E) L-40L+Ck cocultured primary MCL cells (n = 11) were cultured with VNT (24 hours; 25 nM), OBN (48 hours; 0.5 µg/mL), or the sequential combination of OBN and then VNT, paired Wilcoxon test. Cell death was assessed using annexin-V staining. *P < .05, **P < .01, paired Student t test.

OBN counteracts microenvironment-dependent drug resistance in MCL cells. (A) Maver-1 cocultured or not on L-40L cells, and Z138 and JeKo-1 cell lines were treated with VNT for 48 hours at the indicated doses with or without OBN pretreatment (0.5 µg/mL). *Observed value > expected value. (B) Maver-1 cells, in the presence of an L-40L coculture layer, were cultured with OBN (24 hours, 5 µg/mL) alone or in sequential combination with OBN (24 hours, 5 µg/mL) and then VNT (48 hours, 50 nM), cytarabine (AraC; 48 hours, 80 ng/mL) or BDM (48 hours, 100 µM). (C) OBN (48 hours; 0.5 µg/mL) but not RTX (48 hours; 0.5 µg/mL) induced direct cell death in reactivated primary MCL cells (7 days on L-40L+Ck; n = 4); paired Student t test. (D) OBN (48 hours; 0.5 µg/mL) induced direct cell death in L-40L+Ck cocultured primary MCL cells (7 days on L-40L+Ck; n = 12) but not in MCL cell lines (n = 4); Student t test. (E) L-40L+Ck cocultured primary MCL cells (n = 11) were cultured with VNT (24 hours; 25 nM), OBN (48 hours; 0.5 µg/mL), or the sequential combination of OBN and then VNT, paired Wilcoxon test. Cell death was assessed using annexin-V staining. *P < .05, **P < .01, paired Student t test.

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