Magnetic albumin nanospheres that incorporate doxorubicin (M-DOX-BSA-NPs) were prepared previously by our research group to develop magnetically responsive drug carrier system. This nanocarrier was synthesized as a drug delivery system for targeted chemotherapy. In this work, cytotoxic effects of doxorubicin (DOX)-loaded/unloaded or magnetic/non-magnetic nanoparticles and free DOX against PC-3 cells and A549 cells were determined with the MTT test and the results were compared with each other. DOX-loaded magnetic albumin nanospheres (M-DOX-BSA-NPs) were found more cytotoxic than other formulations. The quantitative data obtained from flow cytometry analysis further verified the higher targeting and killing ability of M-DOX-BSA-NPs than free DOX on both of the cancer cell lines. Additionally, the results of cell cycle analysis have showed that M-DOX-BSA-NPs affected G1 and G2 phases. Finally, cell images were obtained using spin-disk confocal microscopy, and cellular uptake of M-DOX-BSA-NPs was visualized. The findings of this study suggest that M-DOX-BSA-NPs represent a potential doxorubicin delivery system for targeted drug transport into prostate and lung cancer cells.
Background and aim: Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. PI3K/AKT pathway is activated in 50% of HCC. The aim of this study was to assess toxicity and efficacy of a new AKT inhibitor (ARQ 092) compared to sorafenib. Method: In vitro experiments were realized with viability, apoptosis and migration assays in 5 different cell lines to analyze the effects of ARQ 092 and sorafenib on the different mechanisms of carcinogenesis. Furthermore, an in vivo study with a diethylnitrosamine (DEN)-induced rat model of HCC on cirrhosis was performed. After 14 weeks of DEN, rats were randomized in 3 groups: control, sorafenib, or ARQ 092 and treated during 6 weeks. Tumor volume and progression were assessed by MRI before treatment, after 3 and 6 weeks of treatment. After euthanasia, pathological analysis of livers was performed assessing tumor numbers and volumes. Results: ARQ 092 showed a dose-dependent decrease in cell viability, induction of apoptosis, and inhibition of migration. In vivo study on 26 rats showed a significantly lower tumor volume in ARQ 092 group: 45.9% of the control versus 60.4% of the control with sorafenib (p = 0.022). Number of tumors per liver was also significantly lower in ARQ 092 group with a mean of 53.9 tumors versus 96.3 tumors in control group (p = 0.001) and 96.8 tumors in sorafenib group (p = 0.015). MRI analysis showed a lower tumor progression in ARQ 092 group with 57.0% versus 155.3% in control group (p<0.0001), and 80.2% in sorafenib group (p = 0.08). Conclusion: ARQ 092 was more significantly control tumor progression in a DEN-induced cirrhotic rat model with HCC compared to sorafenib. Citation Format: Gael S. Roth, Ayca Zeybek, Zusana Macek-Jilkova, Giovanni Abbadessa, Yi Yu, Patrice Marche, Vincent Leroy, Thomas Decaens. Efficacy of AKT inhibitor ARQ 092 compared with Sorafenib in a cirrhotic rat model with hepatocellular carcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B111.
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