Figure 7.

CYD0618 suppresses A2780 xenograft tumor growth in nude mice. A, nude mice bearing A2780 cells were administered vehicle or CYD0618 (10 mg/kg) via once daily intraperitoneal injections for 21 days. Examination of the tumor volumes (A and B) and tumor weights (C) was used to evaluate the effect of CYD0618 on A2780 cells in a xenograft model. Data are expressed as mean ± S.D., n = 6. *, p < 0.05 versus control. D, representative images of pTyr STAT3, Ki67, and Bcl-2 immunostaining as well as the TUNEL-positive cells (green) in tumor tissues. Bar = 50 μm. E, tumor tissues were extracted in RIPA buffer, and Western blotting assay was then performed to assess the expression of pTyr-705 STAT3, STAT3, Bcl-2, cyclin D1. GAPDH was used as a control. F, proposed molecular action model of CYD0618-mediated anti-cancer effect in cancer cells. On covalently binding to Cys-542, CYD0618 blocks the phosphorylation of STAT3 at Tyr-705 via disturbing the binding of STAT3–SH2 domain to the tyrosine-phosphorylated peptide sequences of upstream kinases, leading to an effective suppression on the activation and function of STAT3.