When Cx has been used in a particular tumor cell line, results are rather contradictory among different authors. Raut et al. achieved a reduction in the L3. 6pl pancreatic tumor line impact at only Rapamycin very low concentra tions of Cx injections. Ragel et al. showed that Cx at 1500 ppm orally administered reduced the growth of the tumor line IOMM Lee. Klenke et al. used injections of Cx in a 30 mgkg concentration, obtaining a decrease of an A549 lung tumor, between days 21 and 28. Xu et al. used Panc 1 tumor cell line and observed a decrease in tumor volume and weight when oral Cx was used at 1500 ppm. Harris et al. and Jang et al. generated a tumor using orally administration of DMBA and 1500 ppm of Cx for treatment. Only the first group obtained a significant decrease in tumor volume. Inhibitors,Modulators,Libraries Dai et al.

demonstrated that Inhibitors,Modulators,Libraries Celecoxib 1000 mgkg inhibited rat carcinogenesis and cancer development. Although results and doses may vary for each tumor cell line, our study demonstrated that oral administra tion of Cx at 1000 ppm reduced tumor growth in the TA3 MTXR line. Moreover, since 15th to 19th day there was a significant difference between both groups. It is important to consider the number of animals. Inhibitors,Modulators,Libraries In our study, twelve mice divided in two groups were used. Al though the number of animals was low, the results were significant. Our results propose that Cx reduces angio genesis and proliferation and promotes apoptosis, as reflected in a reduction of tumor growth. However, this effect does not seem to prevent metastasis from primary tumor.

Previously, we have shown that lung metastasis do not decrease in the Cx treated group. Accor dingly with this result, Cx could not reduce proliferation even when Cx reduces microvascular density in pulmo nary metastases, but we do not make a comparison between flank tumor and metastasis. This proposal needs to be clarified in further investigations. Inhibitors,Modulators,Libraries Our results show that Cx inhibits microvascular den sity of a murine AJ mammary tumor and lung metasta sis. The microvascular density comparison succeeded in establishing that there were significant differences in the tumor and lung when treated with Cx, reducing vascular density. Other organs like the spleen and heart did not differ because they were not invaded by tumor cells. The process of tumor angiogenesis is associated with the formation of new blood vessels, which are tortuous, small and abundant in areas of hypoxia.

Inhibitors,Modulators,Libraries Since angiogenic microvessels gene rated by pro angiogenic factors are diminished by the action of Cx, the results are concordant with previous reports correlating angiogenesis and COX 2 activity. Our immunohistochemical study showed that Cx caused a decrease in the presence of KI 67, sellckchem VEGF and increased presence of apoptotic nuclei in TA3 MTXR tumor cells. These effects on the tumor can be explained based on previous studies. Thus, Ghosh et al. reported that COX 2 activity might activate carcinogens.