Tumor volumes were calculated using the following ellipsoid formula2

The same tendency was observed in MCF 7 cells, but no detectable protein level of HER2 was found in MCF 7 cell. In addition, degradation JAK 阻害剤 FDA approved was completely blocked by treatment with the proteasome inhibitor MG132, indi cating that the proteasome system was responsible for FW 04 806 induced client protein degradation. Furthermore, we carried out quantitative real time PCR to test the mRNA expression levels of Akt, HER2, Raf 1, Hsp90, using GAPDH as control. The result showed that FW 04 806 did not block the transcrip tion, but directly acting through inhibition of Hsp90. FW 04 806 inhibits growth, induces cell cycle arrest, induces apoptosis, and downregulates the expression of anti apoptotic proteins The effects of FW 04 806 on cell proliferation were assessed with an MTS assay.<br><br> The proliferation of SKBR3 and MCF 7 cells was LDE225 溶解度 markedly inhibited by FW 04 806, with IC50 values of 12. 11 and 39. 44 uM, respectively. Compared to vehicle only treated controls, FW 04 806 treated cells displayed obvious arrest of cells in the G2M phase after 24 h. The increase in the G2M cell population was accompanied by a concomitant decrease in the population in the S and G0G1 phases of the cell cycle. SKBR3 and MCF 7 cells were treated with FW 04 806 for 24 h and analyzed for apoptotic cell death using an Annexin VFITC Apoptosis Detection Kit. The results revealed a dose dependent induction of necroticlate apoptotic cell death in both cell lines. Caspases, a family of cysteine acid proteases, are cen tral regulators of apoptosis. Western blot analysis re vealed that FW 04 806 caused dose dependent changes in the levels of apoptosis signal proteins.<br><br> The initiator caspase 9, effector caspases, and the PARP precursor exhibited similar reductions, which were ac companied by increases in the levels of their cleaved fragments. These data indicate that FW 04 806 induced apoptosis through caspase dependent path ways in SKBR3 and MCF 7 cells. FW オーダー LY2157299 04 806 inhibits the tumor growth of SKBR3 and MCF 7 tumor xenograft models SKBR3 and MCF 7 human breast cancer xenografts were established to assess the chemotherapeutic poten tial of FW 04 806. The antitumor activity of FW 04 806 at three doses were determined. ADM was used as a positive control. The results demon strated that FW 04 806 inhibited tumor growth in the SKBR3 and MCF 7 xenograft models in a dose dependent manner.<br><br> Compared with the vehicle group, the three increasing doses of FW 04 806 showed, respectively, inhibition of tumor growth at a rate of 39. 1%, 52. 7%, and 67. 5% in the SKBR3 cell line groups and 27. 3%, 39. 8%, 54. 3% in the MCF 7 cell line groups. Notably, the antitumor activity of high dose FW 04 806 was better than positive control group. All animals survived FW 04 806 treatment without appreciable adverse effects in terms of body weight loss or other signs of toxicity during the treatment. Liver and renal function was similar between FW 04 806 treated and control mice. Additionally, lung, liver, heart, and kidneys of mice showed no histological abnormalities at the end of drug treatment. This outcome demonstrates that FW 04 806 was well tolerated. Immunohistochemistry confirmed greater decreases in HER2 expression in the FW 04 806 treated groups compared with the vehicle groups in SKBR3 tumor xenografts.