With this effects, Cx as a COX 2 inhibitor might inhibit angiogenesis, reduces tumor growth and promotes apop tosis. In our study, Cx inhibits tumor growth, micro vascular density and often promote apoptosis of tumor cells resistant to chemotherapy. Kerbel described the signaling pathway of VEGF, a potent proangiogenic factor that produces tumor cells and promotes survival, Inhibitors,Modulators,Libraries proliferation and migration of endothelial cells, critical steps involved in angiogenesis. Our results showed that Cx reduces VEGF production of a murine mammary tumor. Moreover, in some organs where metastasis occurred, such as the lung, VEGF pro duction was abundant. especially in certain outlying areas where tumor cells form nodules but Cx treatment reduced VEGF levels in that area. The idea that VEGF is reduced with the use of Cx is sup ported by Kim et al.

. Rodr��guez et al. and Vaish and Sanyal who defined a relation of B catenin with COX 2 and survivin. Brandao et al. reported that short term COX 2 inhibition by Cx inhibits proliferation reflected by a reduction of Ki 67 positive cells in patients with breast cancer. In our study, Cx at 1000 ppm decreases prolife ration of a murine mammary tumor resistant Inhibitors,Modulators,Libraries to chemo therapy Inhibitors,Modulators,Libraries using the same marker. The association between COX 2 activity and proliferation has been previously proposed. Wu et al. demonstrated that Cx inhibits proliferation and induces apoptosis via PGE2 pathway. Jendrossek proposed that the pro apoptotic effect of Cx is not only mediated by COX 2 inhibition. Cx affects apoptotic signaling at multiple levels such as decreasing expression levels of Mcl 1 and survivin.

Moreover, apoptosis induction by Cx may not depend on the presence of COX 2. Our results demonstrate that Cx promotes apoptosis of murine mammary tumor. Konturek et Inhibitors,Modulators,Libraries al. describes that the binding of PGs to its receptor Inhibitors,Modulators,Libraries promotes evasion of apoptosis through increased survivin and Bcl 2. Moreover, the same binding might induce VEGF expression through hypoxia inducible factor 1 alpha, and cell proliferation and migra tion via MAPK. These mechanisms explain at least in part, the association between VEGF and COX 2PGs. The association between PGs and tumorigenesis is confirmed by Wang and Dubois who showed that PGs are involved in processes of proliferation and phosphatase inhibitor survival, angiogenesis and migration. Moreover, Dai et al. and Brandao et al. showed that Celecoxib inhibits the proliferation of breast cancer. Cx treated group results might be explained at least in part by the effect of Cx on PGs synthesis. 6 days after inoculation, an obvious but significantly smaller tumor was developed. These tumor cells produced low levels of VEGF, because COX 2 action and PG production was much lower.