12 g. The tumor weight of the EGCG-alone group and the DNR-alone group was decreased by 15.7% and 16.8% in comparison with the control group, respectively. The combination of EGCG with DNR reduced the tumor weight by 45.6% in comparison with the control group, and this was significantly lower than that of the EGCG-alone group and the

DNR-alone group (P < 0.01). The antitumor activity of the EGCG and DNR group was higher than the sum of the EGCG-alone and DNR-alone groups (32.5% inhibition), and this suggested synergy between EGCG and DNR. For the Hep3B xenograft, however, the antitumor effect was not obviously different in the EGCG and DNR group and find more the DNR-alone group (Fig. 6C,D). To assess the general toxicity of the combination of EGCG and DNR in animals, we determined and compared the body weights and several biochemical parameters for the same animals receiving

xenografts. For those receiving xenografts of SMMC7721, the EGCG treatment group did not experience substantial decreases in body weight in comparison with the control group (Fig. 7A). The average body weight of the DNR group was 2.31 g lighter than that of the control group, and average body weight of the EGCG and DNR group was 1.34 g lighter than that of the control group (Fig. 7B). Thus, EGCG significantly reversed the weight loss caused by DNR (P < 0.05). The administration of DNR did not affect the alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels http://www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html in serum in comparison with the control group, and these are good indicators of liver disease or damage. Heart injury was tested by markers such as lactate dehydrogenase (LDH), serum creatine kinase MB isoenzyme (CK-MB), malondialdehyde (MDA), and cardiac troponin T (cTnT) in serum. The administration of DNR led to a significant elevation of MDA and cTnT levels but did not affect the levels of the other two markers. The levels of MDA and cTnT were restored to those seen in the control group MCE公司 by a combination with EGCG (Table 1). As shown in Fig. 7C, EGCG also significantly reversed the weight loss caused by DNR in the Hep3B xenograft model (P < 0.05). Similar results were obtained for biochemistry

parameters in serum for EGCG in the Hep3B xenograft model (Table 1). These results suggest that EGCG could increase the safety of DNR therapy in both CBR1-overexpressing and CBR1-underexpressing HCC xenografts in vivo and the coadministration of DNR. Also, EGCG is a promising strategy for overcoming resistance and decreasing toxicity for the anthracycline family of anticancer drugs. Drug resistance is a major challenge in the treatment of malignant tumors. The resistance to the anthracyclines DNR and DOX is mediated in large part by one enzyme, CBR1, which reduces the C13 carbonyl group into alcohols, DNROL and DOXOL, that are not only less active against tumor cells but also cardiotoxic. High levels of CBR1 in HCC cells thus contribute to drug resistance to both DNR and DOX.