The anti-chemoresistant effect and mechanism of MUC1 aptamer–miR-29b chimera in ovarian cancer

• DOI: 10.1016/j.ygyno.2013.07.112
• Publication Date: 2013-08-08T06:16:46Z
• Authors: Furong Dai; Yi Zhang; Xin Zhu; Nianchun Shan; Yuxiang Chen
• Keywords: Chimera (genetics); Aptamer; MUC1

Currently, there are no effective therapies for advanced ovarian cancer. In this study, we aim to determine the anti-tumor effect of MUC1 aptamer-miR-29b chimera in xenograft ovarian cancer models and chemo-resistance tumor model and to further explore the associated mechanism.Xenograft ovarian cancer animal models were established using OVCAR-3, OVCA420, and OVCAR-3-Taxol cancer cells. The chimera (Chi-29b) was delivered through intraperitoneal injections. Tumor growth was evaluated. Gene expression and PTEN methylation were measured.We demonstrated that intratumoral injection of Chi-29b chimera significantly inhibited the growth of xenograft OVCAR-3 tumors through downregulating PTEN methylation, subsequent PTEN expression, as well as downregulating MAPK 4 and IGF1 expressions. In contrast, Chi-29b inhibited tumor growth in OVCA420 tumors by downregulating MAPK 4 & 10 and IGF1 expression without affecting PTEN expression. Intraperitoneal injection of Chi-29b significantly increased apoptosis in paclitaxel-resistant OVCAR-3 cells and inhibited the growth of xenograft OVCAR-3-Taxol tumors. The anti-chemoresistant role of Chi-29b in OVCAR-3-Taxol tumors was associated with the activation of PTEN signaling and downregulation of MAPK 4 and 10 and IGF1 expression.Our study indicated that Chi-29b chimera can effectively exert an anti-tumor effect in xenograft tumor models and an anti-chemoresistant role through inhibiting cancer stem cell activation.