Raji cells were also susceptible to DRB induced cytotoxicity, albeit with some

After MCF 7 and MCF 7 DOX cells were treated with 1 uM doxorubicin for 48 h, terminal deoxynucleotidyl trans ferase mediated dUTP nick end labeling based fluores cence activated cell sorting analysis showed that doxorubicin did not induce apoptosis in MCF 7 DOX cells; however, doxorubicin did induce apoptosis in MCF 7 cells, We further confirmed KU-55933 溶解度 the resistance of MCF 7 DOX cells to doxorubicin by Wes tern blot analysis. Induction of PARP cleavage in MCF 7 cells confirmed that doxorubicin induced apoptosis in these cells. However, PARP was not cleaved in MCF 7 DOX cells treated with doxorubi cin, Acquisition of invasive and metastatic properties in MCF 7 DOX cells Intrinsic or acquired drug resistance results in disease recurrence and metastasis, We analyzed changes in gene expression in doxorubicin resistant MCF 7 DOX cells using DNA array analysis.<br><br> Differentially expressed genes related with invasion are listed in Table 1. We next examined whether MCF 7 DOX cells acquired metastatic オーダー Linifanib properties. First, we measured the enzymatic activities of MMP 9, MMP 2, and uPA in MCF 7 and MCF 7 DOX cells by gelatin and fibrino gen plasminogen zymography. The enzymatic activities of MMP 2, MMP 9, and uPA were markedly higher in MCF 7 DOX cells than in non invasive MCF 7 cells, Increased levels of MMP 9 and MMP 2 expression have been correlated with an invasive pheno type of cancer cells, Thus, we assessed the invasive ness of MCF 7 and MCF 7 DOX cells using in vitro invasion assays. As expected, the MCF 7 DOX cells were significantly more invasive than MCF 7 cells, To test the invasive activity of MCF 7 DOX cells in vivo, we developed a breast cancer model of lung metastasis.<br><br> Three months after injecting MCF 7 DOX cells through the tail veins of balb c nude mice, the mice were killed, and the total number of visible lung tumor nodules per mouse was quantified under a stereomicroscope. LY3009104 JAK Inhibitors Lung tumor nodules were present in the mice injected with MCF 7 DOX cells, while no mouse injected with MCF 7 cells had lung metastases, These results suggest that MCF 7 cells obtained metastatic abilities after acquiring resis tance to doxorubicin.<br><br> Cox 2 mediates invasiveness of MCF 7 DOX cells Recent studies have reported that Cox 2 plays a key role as a regulator of chemotherapy resistance in cancer, In addition, Cox 2 expression plays an important role in the metastatic and invasive abilities of cancer cells, Selec tive inhibition of Cox 2 was shown to suppress the inva sion of oral squamous cells by downregulating an MMP 2 activating mechanism, Therefore, we tested whether invasiveness of MCF 7 DOX cells is related to Cox 2 expression. Western blot analysis showed a high basal level of Cox 2 in doxorubicin resistant MCF 7 DOX cells and metastatic MDA MB 231 cells, Recent studies have reported that Cox 2 overexpres sing cells demonstrate increased inva siveness, Moreover, several studies have suggested that targeting Cox 2 may protect against development of invasive breast cancer, Thus, we tested the effects of a Cox 2 inhibitor on invasion of MCF 7 DOX cells.