![Figure 5. Synergistic killing induced by PKC412 and NFκB inhibition is schedule dependent. (A) Cotreatment with bortezomib (B) (8 nM) and PKC412 (P) (0.5 μM) enhances killing of HMCLs (⊡ indicates NCI-H929; ▪, LP-1) at 72 hours as measured by MTS assay. Graph represents data from 3 individual experiments. Combination treatments were 6 hours P pretreatment then B [P then B] or 6 hours B pretreatment then P [B then P]. NCI-H929, *P < .0015 [P then B] and .001 [B then P], respectively, versus PKC412 alone; OPM2 *P < .001 [P then B] and 0.029 [B then P], respectively, versus PKC412 alone. NCI-H929 #P = .024 [P then B] versus [B then P]; OPM2, #P = .013 [P then B] versus [B then P], Student t test. OPM2 SQ = 3.5 for [P then B] versus PKC412 alone and SQ = 1.6 for [B then P] versus PKC412 alone. (B) Cotreatment with SN50 (S) (25 μg/mL) and PKC412 (P) (1 μM) enhances killing of HMCLs (⊡ indicates NCI-H929; ▪, LP-1). Graph represents data from 3 individual experiments. (C) Seventy-two hours of treatment with PKC412 (0.5 μM) induces apoptosis in primary MM cells, and killing was enhanced by cotreatment with bortezomib (8 nM) (▪ indicates patient MM016; ⊡, patient MM017; □, patient MM021; and [▪], patient MM022). SQs for [P then B] were 1.0, 2.0, 1.6, and 1.0, respectively. Error bars for all graphs indicate SEM.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/109/4/10.1182_blood-2006-05-014092/4/zh80040708260005.jpeg?Expires=1743076762&Signature=wMNhF6DZr2-lPturG6fz6hkXAul6px-n81JaVMNKt0FGrrsvKSw0dsJGJ2BGQOXLMZVx9-HzVfyrr7sCBOfe5SlHkAIPDidgUVdBuz4cTa9wL8YtmJBTgKcEHDi-JK06c-GI18Acm4CdvHG0LhiJtmFRguzJRCksboTIh~dr9hCkjqdiXezVlGkQ9flkEK317PwQNRLDQ3JvQjPPd9AL4WYeeegHfszFavGNK8zXbKnEHIvqnQhJlnJ9glyk7xqgxAWdWr1thM~wxFM3nJQ~TFZvqI9XXlNQI~6Md84JUynPVRDOddTZl0Uq3owcLhn-zGkXt-PZXLHxBgLoVbnKnA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Synergistic killing induced by PKC412 and NFκB inhibition is schedule dependent. (A) Cotreatment with bortezomib (B) (8 nM) and PKC412 (P) (0.5 μM) enhances killing of HMCLs (⊡ indicates NCI-H929; ▪, LP-1) at 72 hours as measured by MTS assay. Graph represents data from 3 individual experiments. Combination treatments were 6 hours P pretreatment then B [P then B] or 6 hours B pretreatment then P [B then P]. NCI-H929, *P < .0015 [P then B] and .001 [B then P], respectively, versus PKC412 alone; OPM2 *P < .001 [P then B] and 0.029 [B then P], respectively, versus PKC412 alone. NCI-H929 #P = .024 [P then B] versus [B then P]; OPM2, #P = .013 [P then B] versus [B then P], Student t test. OPM2 SQ = 3.5 for [P then B] versus PKC412 alone and SQ = 1.6 for [B then P] versus PKC412 alone. (B) Cotreatment with SN50 (S) (25 μg/mL) and PKC412 (P) (1 μM) enhances killing of HMCLs (⊡ indicates NCI-H929; ▪, LP-1). Graph represents data from 3 individual experiments. (C) Seventy-two hours of treatment with PKC412 (0.5 μM) induces apoptosis in primary MM cells, and killing was enhanced by cotreatment with bortezomib (8 nM) (▪ indicates patient MM016; ⊡, patient MM017; □, patient MM021; and [▪], patient MM022). SQs for [P then B] were 1.0, 2.0, 1.6, and 1.0, respectively. Error bars for all graphs indicate SEM.
