[doi: 10.5505/2017ichc.OP-53]Effects of Paclitaxel, Bevacizumab and Metformin on PI3K/AKT pathway and Angiogenesis in MDA-MB 231 Breast Cancer Cell LineFatma Firat1, Elgin Turkoz Uluer1, Sevinç Inan22Department of histology embriyology, IZMIR ECONOMY UNIVERSITY, MANISA, TURKEY Breast cancer is the most common cancer worldwide. PI3K/AKT and Ras/Raf/MEK/ERK pathways are frequently dysregulated in cancer. In this study we aimed to investigate effects of Metformin which is used in diabetes treatment, chemotherapeutic drug Paclitaxel and anti angiogenic drug Bevacizumab on metastatic breast cancer cells MDA-MB-231 via indirect immunohistochemistry (IHC). MDA-MB 231 cells were cultured in RPMI-1640 medium. After growing, we divided cells as bevacizumab (B), paclitaxel (P), metformin (M), (B+M), (P+M) ve (B+P+M) groups and the no treatment-control group and the IC50 dose of drugs was applied and the effect of 24th hour was evaluated. Cells were incubated with anti-AKT, anti-PI3K, anti-ERK, anti-PERK and anti-VEGF primary antibodies. Cells viewed under light microscope (Olympus BX40). The distribution of immunohistochemical intensities of primary antibodies were scored as mild (+), moderate (++), strong (+++) and very strong (++++). After counting the percent of positive staining cells, statistical significance was determined by ANOVA test. Significance was defined as p<0.05. According to the IHC evaluation, AKT, PERK, ERK and VEGF immunoreactivities were increased when compare to the control group in B, P groups. In M treatment group ERK, VEGF and AKT immunoreactivities were decreased and PI3K was increased when compare to the other groups. In B+M group ERK, VEGF, AKT and PI3K immunoreactivities were increased, similer to the P+B and B+M+P groups ERK, AKT and PI3K immunoreactivities were incresed. And in M+P group PERK and ERK were decreased. According to the immunohistochemical evaluation; treatment of B+M+P leads to MDA-MB 231 cells for 24 hours. However in recent studies, usage of antidiabetic drug M alone and/or combination with chemotherapeutic drugs showed controversial effects. In this study it was shown that alone administration of M was not effective while combination with P and B is more effective via AKT and ERK pathways. |