Followed prior to treatment with Prasugrel P2X receptor inhibitor docetaxel or vorinostat significantly inhibited cell growth belinostat CG200745. The indices of the combination of these combinations is that treatment with docetaxel followed by CG200745 is the synergistic. To determine whether the combination of docetaxel and CG200745 was synergistic in detail, we exposed DU145 cells to drugs while keeping constant the ratio Ratio of drugs. The analysis of the dose-response relationship and isobolograms showed that the sequential treatment was synergistic, but the combination of h Higher concentrations of each drug. To investigate the type of cell death induced by combined treatment, we performed flow cytometry of DU145 cells with docetaxel either alone or in combination and treated CG200745. DU145 treated with single CG200745 has entered Born population increased in the G1 Ht fa Significantly, when compared to treatment with docetaxel alone. Pre DU145 with Docetaxel followed by treatment CG200745 showed a further increase in Bev Lkerung in G1. Histograms was shown anblotting caspase that CG200745-induced apoptosis of prostate cancer. These results show the M Possibility of using these stove HDACI CG200745 for the treatment of prostate cancer hormonabh Ngigen and two hormone independent. Since HDACIs including normal CG200745 showed growth inhibitory effect when monaural HRPC treated cells in our study, and it was reported that HDACIs enhance the antitumor effect of docetaxel, we examined the F Ability of CG200745 in potentiation of the activity t of docetaxel, the most effective chemotherapeutic agent for HRPC is well. The sequential treatment with docetaxel followed by CG200745 showed growth inhibition when tested in DU145 cells. In addition, CI plot and isobologram showed a combination of docetaxel and the synergistic effect of CG200745. In addition, docetaxel showed IC plus better synergies CG200745 compared with vorinostat or belinostat. These results demonstrate the usefulness of a sequential treatment with docetaxel followed by CG200745 in the treatment of HRPC. Zus Tzlich we examined caspase activation and Bcl-2 protein levels of the family in an effort to other mechanisms of cell death in kl Ren.
Levels of activated caspase, 3 and were obtained by combined treatment with docetaxel and CG200745 indicating that the drug caused apoptosis pathways through both extrinsic and intrinsic erh ht. Combination therapy also reduces the anti-apoptotic proteins Mcl 1L, Mcl 1s, and Bcl XL. Since previous studies have demonstrated the effectiveness of aid belinostat in combination with docetaxel enzalutamide CYP17 Inhibitors demonstrated in vivo, and all of our in vitro experiments have shown that the antitumor effect of combination treatment with docetaxel and CG200745 to HRPC cells, we examined whether CG200745 the antitumor effect of docetaxel in Nacktm potentiated mice injected with DU145 cells. We compared the effects of the CG200745 belinostat before the combined treatment. W While the IC 50 of CG200745 was less than that of belinostat in DU145 cells in vitro, was the anti-tumor effect of CG200745 Similar belinostat in vivo. Therefore, we have next explained Utert the effect of combined treatment in DU145 xenograft mouse model. The combined treatment significantly decreased tumor volume compared to the single treatment of each drug.