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Ated cells (P 0.05). (e) Morphological look of breast cancer cells treated
Ated cells (P 0.05). (e) Morphological look of breast cancer cells treated with Bcl-2 siRNA by phase contrast microscopy (72 hour-MCF7) at 10 and 40magnification.Therapeutic silencing of Bcl-2 by NL-Bcl-2-siRNA enhances the antitumor efficacy of chemotherapy in an ER(-) MDA-MB-231 model To evaluate the in vivo effects of siRNA-induced Bcl-2 silencing on the antitumor efficacy of chemotherapy, we also combined NL-Bcl-2 siRNA with weekly doxorubicin (4 mg kg, i.p.), probably the most generally used chemotherapeutic agents. Mice that received the combination of NL-Bcl2-siRNA and doxorubicin had drastically smaller tumors than the control group that received NL-control siRNA and doxorubicin (P = 0.006; Figure 3b, c). As expected, a marked inhibition of Bcl-2 protein expression was AMPA Receptor supplier observed in MDAMB-231 tumors right after 4 weeks of NL-Bcl-2 siRNA therapy (Figure 3d). No Bak manufacturer toxicity was observed in mice exposed to NL-Bcl-2 siRNA for four weeks (Figure 3e). Mice appearedhealthy and active and showed no apparent unwanted side effects just after therapy with NL-Bcl-2 siRNA (Figure 3e). The imply weight within the NL-Bcl-2 siRNA-treated group was 27.five 0.7 g and didn’t statistically differ from that within the NL-controlsiRNA group (28.six 0.five g). Even so, as anticipated, mice that received doxorubicin were slightly smaller soon after remedy. Furthermore, we also sought to decide whether the silencing of Bcl-2 by siRNA can boost the activity of chemotherapeutic agents other than doxorubicin and assessed the effects of paclitaxel in combination with Bcl-2 siRNA. The mixture of Bcl-2 silencing with paclitaxel substantially decreased the growth and colony formation of MDA-MB-231 cells in vitro, suggesting that siRNA-mediated Bcl-2 silencing can boost the efficacy of other frequently used chemotherapeutic agents.moleculartherapy.orgmtnaBcl-2 Silencing by siRNA Inhibits Breast Cancer Tumors Tekedereli et al.aNL: Cont-siRNA 0.15 mgkgDay two Bcl-2 siRNA Bcl-2 siRNA 0.075 mgkg 0.15 mgkgDay four Bcl-2 siRNA 0.15 mgkgDay 6 Bcl-2 siRNA 0.15 mgkgBcl-2 -ActinbBcl-2 expression ( )0 NL:Cont-siRNA 0.15 mgkgBcl-2 siRNA Bcl-2 siRNA 0.075 mgkg 0.15 mgkg DayBcl-2 siRNA 0.15 mgkg DayBcl-2 siRNA 0.15 mgkg DayFigure 2 Time- and dose-dependent kinetics of Bcl-2 inhibition by systemically administered nanoliposomal (NL)-Bcl-2-siRNA in MDA-MB-231 orthotopic xenograft model. (a) Mice-bearing MDA-MB-231 tumors were injected with a single i.v. dose of NL-ControlsiRNA or NL-Bcl-2-siRNA (0.075 or 0.15 mg siRNAkg from tail vein) and tumors had been removed on days 2, 4 and 6. Inhibition of Bcl-2 protein expression was detected by western blot analysis of tumor lysates. (b) Inhibition of Bcl-2 protein expression by densitometric analysis of bands shown in 1A tumors.Therapeutic targeting of Bcl-2 by NL-Bcl-2-siRNA inhibits tumor development of ER() MCF-7 breast tumors and increases the efficacy of chemotherapy Simply because no published study has assessed the in vivo effects of siRNA-mediated therapeutic Bcl-2 silencing in ER() breast tumors, we also investigated the antitumor efficacy of NL-siRNA therapy in an MCF-7 orthotopic tumor model in nude mice. About two weeks following tumor cells were injected into their mammary fat pads, mice with equally sized tumors have been randomly split into groups and offered either NL-Bcl-2 siRNA or NL-control siRNA (0.15 mg siRNA kg, i.v. tail vein, twice per week) for four weeks. Tumor development was drastically inhibited in mice treated with NL-Bcl-2 siRNA (Figure 4a). The imply tumor weight within the NL.

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