Cox 2 mediates invasiveness of MCF 7/DOX cells Recent studies have reported that Cox 2 plays a key www.selleckchem.com/products/Pazopanib-Hydrochloride.html role as a regulator of chemotherapy resistance in cancer. In addition, Cox 2 expression plays an important role in the metastatic and invasive abilities kinase inhibitor Rapamycin of Inhibitors,Modulators,Libraries cancer cells. Selec tive inhibition of Cox 2 was shown to suppress the inva sion of oral squamous Regorafenib side effects cells Inhibitors,Modulators,Libraries by downregulating an MMP 2 activating mechanism. Therefore, we tested whether invasiveness of MCF 7/DOX Inhibitors,Modulators,Libraries 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 Inhibitors,Modulators,Libraries 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, Inhibitors,Modulators,Libraries we tested the effects of a Cox 2 inhibitor on invasion of MCF 7/DOX cells. Treatment of MCF 7/COX cells Inhibitors,Modulators,Libraries with the Cox 2 inhibitor NS398 decreased their invasive potential, indicating Inhibitors,Modulators,Libraries that Cox 2 expression contributes Inhibitors,Modulators,Libraries to the invasive activity of MCF 7/DOX cells. We next determined the effects of the Cox 2 inhibitor NS398 on activities of MMP 9, MMP 2, and uPA secreted from MCF 7/DOX cells using Inhibitors,Modulators,Libraries plasminogen/fibrinogen and gelatin zymography assays. We found that the activity of MMP 9 and uPA was inhibited by 50 uM NS398, a con centration that did not affect MCF 7/DOX cell prolif eration.

The effect of Cox 2 expression on invasiveness of MCF 7/DOX cells was confirmed by blocking Cox 2 expression using siRNA.

Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries Consistent with the results of the Cox 2 inhibitor experiment, transfection of siRNA targeting Cox 2 sup pressed migration of MCF 7/DOX cells in an in vitro migration assay. Effect Inhibitors,Modulators,Libraries of the EGFR pathway on Cox 2 mediated invasion of MCF 7/DOX cells Inhibitors,Modulators,Libraries Having identified Cox 2 as an important regulator of invasiveness of MCF 7/DOX cells, we next asked which upstream pathway modulates the expression Inhibitors,Modulators,Libraries of Cox 2 in this cell line. Because EGFR has been reported to regu late Cox 2 expression, we hypothesized that activa tion of the EGFR pathway may induce Cox 2 expression.

First, we examined the basal expression level of EGFR in a subset of breast cancer cell lines.

Western blot Inhibitors,Modulators,Libraries analysis showed high levels of EGFR expression in the doxorubicin resistant MCF 7/DOX and MDA MB 231 cells, which were invasive and had elevated Cox 2 expression.

We http://www.selleckchem.com/products/dorsomorphin-2hcl.html next tested the role of the EGFR pathway on induction of Cox 2 expression by treating cells with leave a message Ganetespib IC50 EGF and blocking these pathways using EGFR specific siRNA. Cox 2 expression was markedly suppressed when both MCF 7/DOX and MDA MB 231 cells were transfected with EGFR specific siRNAs. In addition, Western blot analyses of MCF 7/DOX cells revealed that Cox 2 expression was induced within 2 h of EGF treatment.