The effects of metformin and PCL-sorafenib nanoparticle co-treatment on MCF-7 cell culture model of breast cancer.

Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and sorafenib are well-known therapeutics in breast cancer. In the present study, we combined sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. The MCF-7 cells were treated with metformin, sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by real-time PCR. The results showed that MCF-7 cells treated with metformin/sorafenib and PCL-sorafenib/metformin co-treatment contributed to 50% viability compared to the untreated group. Moreover, PI and Annexin V staining tests showed that the cell viability for metformin/sorafenib and PCL-sorafenib/metformin was 38% and 17%, respectively. Furthermore, sorafenib/metformin and PCL-sorafenib/metformin lead to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2 and BAX genes and altered the cell cycle. Together, the combination of PCL-sorafenib/metformin and sorafenib/metformin increased sorafenib absorption at lower doses and also led to apoptosis and oxidative stress increases in MCF-7 cells.

Optimization of a recombinant BlaR-CTD protein formulation using the response surface methodology.

The sequence of a carboxy-terminal of the ß-lactam sensor-transducer protein (BlaR-CTD) from Bacillus licheniformis ATCC14580 was extracted from US7745193B2 patent and expressed in E. coli using pColdI vector as a soluble His-tag recombinant protein. In this study, several excipients were used to improve the stability of recombinant BlaR-CTD and obtain the optimal formulation for this protein using response surface methodology (RSM)/ Central Composite Design (CCD). Total protein concentration was measured by UV spectroscopy and the Bradford test. A total of 7 various factors were designed using four different excipients including Glycerol, Sucrose, Triton x-100, and Tween-20, and three different buffers like Tris, Borate, and PBS. By obtaining suitable excipients and buffer i.e. glycerol and sucrose, pH ranging from 7 to 9 were evaluated. The pH 7.62, glycerol 15.35%, and sucrose 152.52 mM were determined as the most suitable for improving the thermal stability of recombinant BlaR-CTD.