Effect of ulinastatin on growth inhibition, apoptosis of breast carcinoma cells is related to a decrease in signal conduction of JNk-2 and NF-κB

The cell lines cultured were divided into four groups: 1) control group, 2) UTI group, 3) TXT group, and 4) UTI+TXT group. The method of MTT essay, flow cytometry, and RT-PCR were used to detect cell proliferation, cell apoptosis, and expression of IGF-1R, PDGFA, NGF, NF-κB, JNk-2, respectively. The growth of xenografted tumor in nude mice was used to calculate the anti-tumor rate. Immunohistochemistry staining (SP) was used to detect the expression of IGF-1R, PDGFA, NGF, ki-67, caspase-3, JNk-2, and NF-κB.Proliferation of human breast cancer cells and MDA-MB-231 cell lines, and growth rate of xenografted tumor decreased in order of UTI+TXT > TXT > UTI > control, apoptosis increased in the order control < UTI < TXT < UTI+TXT. The gene expression and protein expression of IGF-1R, PDGFA, NGF, NF-κB and JNk-2 in breast cancer cells was inhibited by UTI and TXT.UTI 1) inhibits the proliferation of human breast cancer cells and the growth of xenografted tumors, 2) induces cancer cell apoptosis, and 3) enhances the anti-tumor effect of TXT. This mechanism might be related to decreasing signal transduction of JNk-2 and NF-κB, and then expression of IGF-1R, PDGFA, NGF.Breast cancer is a major malignant tumor threatens women's health. It is the second leading cause to women's death [1]. Ulinastatin (UTI), a physiological urinary trypsin inhibitor, inhibits a variety of proteases. It is widely used in treatment of inflammatory diseases, including disseminated intravascular coagulation, shock, and pancreatitis [2,3]. Our previous study showed that UTI exerts significant inhibitory effects on 1) the proliferation and invasion of human breast cancer cell lines MCF-7 and MDA-MB-231, 2) the growth of MCF-7 transplanted tumor in nude mice, 3) the gene and protein expression of CXCR4 and MMP-9 in breast cancer cells; UTI also enhances the anti-tumor effect of the chemotherapy drug cyclophosphamide [4,5]. TXT is the most effective chemotherapy drug to treat breast cancer. It is widel