In vivo effect of tamoxifen on human breast cancer cell lines in xenograft nude mice. (A) Tamoxifen treatment decreased the size of MDA-MB-468 tumors (left) but did not affect HCC-1937 tumor cell growth (right). Points, mean values (n = 6); bars, SE; *P < 0.05. Mice received either 100 mg/kg body weight tamoxifen citrate administered orally three times weekly or vehicle (1× phosphate-buffered saline), as described in the Methods section. (B) Western blot analysis of the expression levels of cancerous inhibitor of protein phosphatase 2A (CIP2A), phospho-Akt (p-Akt) and Akt in MDA-MB-468 and HCC-1937 xenografts treated with control or tamoxifen. (C) Body weight of xenograft mice bearing MDA-MB-468 (top) and HCC-1937 (bottom) tumors. Points, mean values (n = 6); bars, SD. (D) Schema of the molecular mechanism of the action of tamoxifen on the CIP2A/PP2A pathway. By inhibiting CIP2A, tamoxifen restores protein phosphatase 2A (PP2A) activity downregulating p-Akt and leading to subsequent cell apoptosis.