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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
Furong
F
Dai
Yi
Y
Zhang
Xin
X
Zhu
Nianchun
N
Shan
Yuxiang
Y
Chen
D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs; D018396:Mucin-1 / Q000008:administration & dosage* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000628:therapy*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D052157:Aptamers, Nucleotide; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D018396:Mucin-1; D011993:Recombinant Fusion Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017239:Paclitaxel
Animal model; Aptamer; Cancer stem cell; Ovarian cancer; PTEN; miRNA