Pin1 downmodulation sensitizes breast CSCs to chemotherapeutic treatment in vitro and in vivo.
A Pin1 knockdown synergizes with chemotherapy treatment to block breast CSCs' self-renewal. Percentage of M2FE of control MDA-MB-231-pLKO-shPin1 cells (Ctrl) compared to shPin1-induced cells (DOX) treated with indicated drugs or PBS. Means and standard deviations are indicated, P-values are * = 0.001, **< 0.0003 (t-test, n = 3).
B Pin1 knockdown synergizes with paclitaxel to block breast cancer growth. Tumor growth of MDA-MB-231 xenografts espressing the indicated shRNAs and treated with paclitaxel (grey bars) or left untreated (PBS) (black bars). Means and standard deviations are indicated, P-values are *** < 0.0003 (t-test, n = 12).
C Pin1 knockdown blocks chemotherapy-induced breast CSCs' expansion in vivo. Histogram representing the Aldefluor mean fluorescent intensity (MFI) of cells from control- and shPin1 MDA-MB-231 xenografts treated with Paclitaxel or PBS. Means and standard deviations are indicated, P-values are * = 0.001 (t-test, n = 3 for each condition).
D Pin1 knockdown induces reversal of EMT and cell death in breast cancer xenografts in combination with paclitaxel. Western blot analyses of tumor xenografts from (B).
E Expression of stable N1-ICD-dPEST rescues resistance to paclitaxel treatment in Pin1 silenced cells. Percentage of M2FE of control (black bars) or Pin1 shRNA (grey bars) expressing MDA-MB-231 cells transduced with empty (–) or N1-ICD-dPEST (+) expressing vectors, treated with Paclitaxel (+) or PBS (–). Means and standard deviations are indicated, P-values are **0.0001, ***<0.00003 (t-test, n = 3).