Therapeutic evaluation of SC-1 and SC-43 on breast cancer xenograft tumor growth
. A, SC-1 and SC-43 show significant antitumor effects on MDA-MB-468 tumors. Growth curves of MDA-MB-468 tumors treated with vehicle, sorafenib, SC-1 and SC-43. Points, mean (n = 6); bars, SE. B, left, western blot analysis of p-STAT3 and STAT3 in MDA-MB-468 tumors. Right, the activity of SHP-1 in MDA-MB-468 tumors. Tumors were harvested 28 days after treatment and assayed for molecular events by western blotting and for SHP-1 activity. Columns, mean; bars, SD (n = 3). *P <0.05. C, overexpressed STAT3 in MDA-MB-468 tumors shows a significant protective effect against treatment with SC-43. Left, p-STAT3 and STAT3 expressions in STAT3-overexpressed and in empty vector- transfected MDA-MB-468 cells. Middle, growth curves of STAT3-overexpressed MDA-MB-468 tumors treated with vehicle and SC-43. Points, mean (n = 6); bars, SE. Right, western blot analysis of p-STAT3 and STAT3 in STAT3-overexpression MDA-MB-468 tumors treated with vehicle or SC-43. Tumors were harvested 28 days after treatment and assayed for molecular events by western blotting. D, body weight of xenograft mice bearing MDA-MB-468 tumors (left) and STAT3-overexpression MDA-MB-468 tumors (right) during the in vivo experiment. Points, mean (n = 6); bars, SE. Female NCr athymic nude mice (four to six weeks of age) were used for experiments (A) to (D). Mice were treated with sorafenib, SC-1 or SC-43 (10 mg/kg body weight) per os daily. Controls received vehicle. E, scheme of SHP-1 mediated drug mechanism of SC-1 and SC-43 in breast cancer cells.