Combined treatment of glibenclamide and CoCl2 decreases MMP9 expression and inhibits growth in highly metastatic breast cancer

BACKGROUND To observe the influence of combination treatment with glibenclamide and CoCl(2) on the growth and invasiveness of TA2 breast cancer, and to detect the protein and mRNA expression of MMP9. METHODS 50 adult female TA2 mice were randomly divided into 5 groups including DMSO control, CoCl(2), glibenclamide, CoCl(2) + glibenclamide and paclitaxel. All of these mice were inoculated with TA2 spontaneous breast cancer cells in the left groin. Nine days after inoculation the tumor could be palpated. Different treatments for each group were then subcutaneously administered near the tumors on the 9th and 14th days after injection. Tumor size was measured to determine the growth curve. All mice were sacrificed on the 18th day after initial inoculation and tumor tissues were collected. Some fresh tissues without necrosis were stored at -80°C for mRNA detection and the other tumor tissue was fixed with 10% formalin for H&E and immunohistochemical staining. RESULTS The growth rate of tumor cells in the CoCl(2) + glibenclamide group was lower than that seen in the other groups. On the 14th day, the average volume of tumor in the CoCl(2) + glibenclamide group was the lowest and the difference has statistical significance (P < 0.05), while the differences among the CoCl(2), glibenclamide and paclitaxel had no statistical significance. The mean percentage of cells expressing MMP9 and PCNA was the lowest in the CoCl(2) + glibenclamide group (P < 0.05). MMP9 mRNA expression paralleled MMP9 protein expression in these groups (P < 0.05). CONCLUSIONS Combined treatment with glibenclamide and CoCl(2) inhibits TA2 spontaneous breast cancer growth and invasiveness with effects similar to paclitaxel.