[PubMed] [Google Scholar] 13. of MOC31PE alone and in combination with chemotherapy In the present experiments, the cytotoxicity of paclitaxel, carboplatin, and cisplatin, alone and in combination with MOC31PE was examined in B76 and 2774 cells (Figure ?(Figure1A).1A). The B76 cells were carboplatin resistant (IC50 was not reached even at 72h, data not shown), moderately sensitive towards paclitaxel (IC50 was not reached at 24h, Figure ?Figure1A)1A) and IC50 was 25 nM at 72h (not shown) and cisplatin sensitive (IC50 16.5 M, not demonstrated). The 2774 cells exhibited moderate level of sensitivity to paclitaxel, but were resistant to both platinum compounds. In both cell lines, cell viability was reduced by 25-30% upon incubation with a low concentration of MOC31PE (10 ng/ml at 24h), and for combination experiments, this concentration of MOC31PE was used, which inhibited protein synthesis by 50% in both cell lines (Supplementary Number 1 for 2774 and B76 ). The combination of MOC31PE and paclitaxel caused a 50% reduction in cell viability in both cell lines compared to the monotherapies (25-30%) (p 0.05), signifying an additive effect of combing the medicines. Co-treatment with MOC31PE and carboplatin reduced cell viability of B76 cells by approximately 20% compared to treatment with MOC31PE only (p 0.05), but this effect was not observed in 2774. For the combination of MOC31PE and cisplatin, there was a nonsignificant tendency towards reduced viability. Notably, the results display that MOC31PE cytotoxic effect was not antagonized in combination with standard chemotherapy. Open in a separate window Number 1 MOC31PE in combination with paclitaxel causes additive cytotoxicity effectiveness of MOC31PE Administration of MO31PE (150 g/kg) i.p. significantly prolonged survival in the B76 model compared to vehicle treated animals, having a MST of 44 days (SD 4.2) versus 24 days (SD 1.0), respectively (p 0.01; Number ?Number3A).3A). This dose of MOC31PE was well tolerated with no indications of toxicity. In the 2774 model, MOC31PE i.p. (150 g/kg) improved survival significantly (53 days, SD 2.4) compared to vehicle (23 days, SD 1.3, (p 0.01)) (Number ?(Figure3B).3B). In addition, a reduced ascites accumulation were record, with only 2 out of 6 animals showing with measurable amount of ascites (3.7 ml and 2 ml), whereas all 6 vehicle treated mice had ascites (3.9 ml, SD 2.3). Notably, administration of MOC31PE (150 g/kg i.p.) mainly because a single treatment dose, significantly long term the MST of the treated mice was compared SIRT-IN-1 to the vehicle group, (p 0.01) whether the treatment was started on day time 7 (41 days, SD 2.5) or on day time 11 (34 days, SD 2.8) (Number ?(Figure3B3B). Open in a separate window Number 3 MOC31PE raises survival of mice with B76 and 2774 peritoneal metastasesKaplan-Meier survival curves of mice injected i.p. with (A) B76 and (B) 2774 cells. B76 animals were treated i.p. 24 h later on with one dose of MOC31PE (150 g/kg) or vehicle whereas 2774 mice received a single treatment dose either day time 1, day time 7 or day time 11 after injection of the tumor cells. SIRT-IN-1 The mean survival time (MST) is definitely summarized in the furniture under the graphs. effectiveness of MOC31PE in combination with chemotherapy Paclitaxel (7.5 mg/kg) treatment alone did not influence animal survival (22 days, SD 5.0) in the B76 model compared to vehicle (22 days, SD 1.1, p 0.05), while a low dose of MOC31PE (50 g/kg) was still efficacious (31 days, SD 5.0) (Number ?(Figure4A).4A). Combining MOC31PE and paclitaxel significantly improved MST (35 days, SD 5.2) with an effectiveness much like MOC31PE alone. Open in a separate window Number 4 effectiveness of MOC31PE, paclitaxel and mitomycin C as solitary providers and in combination experimentsKaplan-Meier survival curves of groups SIRT-IN-1 of at least five mice injected with B76 (A) or 2774 (B) cells and treated i.p. 24 h later on with single doses of MOC31PE and paclitaxel (7.5 mg/kg) alone and in combination, with vehicle as control. The MOC31PE dose was low in B76 mice (50 g/kg) and high in 2774 mice (150 g/kg). The mean survival instances (MST) and p-values are summarized in the furniture under the graphs. (C) Rabbit polyclonal to HPN Kaplan-Meier survival curves of groups of at least five mice inoculated with B76 cells and treated i.p. 24 h later on with single doses of a low MOC31PE (32 g/kg) and a.