RESUMO
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.
RESUMO
In this study, we reported the expression and potency of the recombinant H1N1 hemagglutinin (HA) vaccine as our in-house vaccine in a BALB/c mouse model. Recombinant H1N1 HA was produced in SF9 cell line, purified and formulated in MF59 adjuvant. Experimental mice were injected on days 0 and 14 with MF59-formulated vaccine, alum-based vaccine, and phosphate-buffered saline (PBS). Interleukin (IL)-2, IL-4, and interferon (IFN)-γ were assessed with commercial enzyme-linked immunosorbent assay (ELISA). Antibody responses and cytotoxic T lymphocyte (CTL) activity were assessed by hemagglutination inhibition and granzyme B ELISA, respectively. Moreover, the mice were challenged to show the vaccine efficacy. A considerable rise in IFN-γ and IL-4, as well as IFN-γ/IL-4 ratio, was observed in comparison with the alum-based vaccine and PBS group. Furthermore, our candidate vaccine showed superiority in humoral immune responses and CTL activity versus the alum-based vaccine and PBS group. The challenge showed that the survival rate in the vaccinated groups revealed a significant increase as compared with that in the PBS group. In conclusion, our candidate vaccine showed a robust Th1 response and CTL activity the alum-based vaccine. Moreover, a significant humoral immune response and a higher survival rate were detected in our vaccine as compared with the alum-based vaccine. It seems that the superiority of the MF59-based vaccine is due to the type of vaccine formulation in the candidate vaccine.
