Synergistic effects of Endostar combined with ß-elemene on malignant ascites in a mouse model.

To explore an effective combination therapy for malignant ascites, the therapeutic value of the combination of Endostar, a modified recombinant human endostatin, and ß-elemene, an active component of a traditional Chinese herb, in an H22 mouse malignant ascites model was investigated. The optimal dose combination of Endostar and ß-elemene was determined by evaluating the inhibition of ascites volume and increase in the survival rate of the mice. Other therapeutic effects and the underlying mechanisms were investigated under the optimal dose combination (8 mg/kg Endostar plus 100 mg/kg ß-elemene). The mice were randomly divided into four treatment groups and received intraperitoneal injection once a day for eight days: control (0.9% normal saline), Endostar (8 mg/kg), ß-elemene (100 mg/kg) or optimal dose combination (8 mg/kg Endostar plus 100 mg/kg ß-elemene), respectively. The results of this study revealed that the combination therapy had significant synergistic effects on the inhibition of ascites formation and a deceased number of tumor cells and protein levels in ascites compared with the results of treatment with a single agent. A decreased peritoneal microvascular permeability and reduction in VEGF, MMP-2 and hypoxia inducible factor 1α (HIF1α) was noted in the combination group, when compared with single agent treatment. These studies found that in the ascitic tumor cells, the protein levels of VEGF and MMP-2, as well as levels of VEGF mRNA, were significantly inhibited by the combination therapy. The potentiating effects of the combination of Endostar with ß-elemene suggest that this novel therapy may yield an effective therapy for the treatment of malignant ascites.

[Therapeutic features of endostar, a modified endostatin, on ascites tumor in mice].

OBJECTIVE: To investigate the effect of endostar in controlling ascites tumor formation in mice. METHODS: Mouse models bearing ascites tumors were established via intraperitoneal injection of H22 and S180 cell lines. Eighty-eight ICR mice were randomly assigned into 4 groups, namely the control group (0.9% normal saline) and 3 endostar groups with 8 mg/kg endostar administration daily, every other day or every two days. The peritoneal membrane permeability of the mice was assessed using Evan blue staining. The body weight curve of mice was drawn, and the cumulative ascites volume and number of red cells and tumor cells in the malignant ascites were determined. The survival of the mice was evaluated to assess the therapeutic effect of endostar. RESULTS: Compared with the control group, the mice receiving daily endostar injection showed obviously lower ascites accumulation and peritoneal capillary permeability (P<0.05) with reduced count of ascites tumor cells and red cells and tumor burden of the abdominal cavity. The mice with daily endostar injection also showed longer survival than the control group. CONCLUSIONS: Continuous intraperitoneal injection can be the optimal means for endostar administration for treatment of malignant ascites.

Protolimonoids from Melia toosendan.

Toosendanone A (1), a new euphane (tirucallane)-type triterpene bearing a five-membered ring in the side chain and the first cyclopentanyl protolimonoid, was isolated from the bark of Melia toosendan, along with two new tirucallanes, toosendanic acids A (2) and B (3). The structure and absolute configuration of compound 1 was elucidated by spectroscopic data interpretation and X-ray diffraction analysis. Compounds 1-3 were evaluated for cytotoxicity against a small panel of cancer cell lines.

3D-QSAR studies of boron-containing dipeptides as proteasome inhibitors with CoMFA and CoMSIA methods.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed for a series of dipeptide boronate proteasome inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 46 molecules served to establish the models. The optimum CoMFA and CoMSIA models obtained for the training set were all statistically significant with cross-validated coefficients (q(2)) of 0.676 and 0.630 and conventional coefficients (r(2)) of 0.989 and 0.956, respectively. The predictive capacities of both models were successfully validated by calculating a test set of 13 molecules that were not included in the training set. The predicted correlation coefficients (r(2)(pred)) of CoMFA and CoMSIA are 0.963 and 0.919, respectively. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of beta5 subunit of 20S proteasome, which suggests that the 3D-QSAR models constructed in this paper can be used to guide the development of novel dipeptide boronate inhibitors of 20S proteasome.