Reversal of Paclitaxel Resistance in Epithelial Ovarian Carcinoma Cells by a MUC1 Aptamer-let-7i Chimera

The purpose of this study was to establish tumor tissue specific delivery of let-7i miRNA to reverse paclitaxel-induced chemoresistance. A chimera that combines MUC1 aptamer and let-7i miRNA was tested in OVCAR-3 ovarian cancer cells. Results demonstrated that the chimera can specifically be deliver...

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Bibliographic Details
Published in:Cancer investigation 2012-10, Vol.30 (8), p.577-582
Main Authors: Liu, Nenghui, Zhou, Changju, Zhao, Jingfeng, Chen, Yuxiang
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Apoptosis - genetics
Aptamer
Aptamers, Nucleotide - genetics
Aptamers, Nucleotide - metabolism
Artificial Gene Fusion
Base Sequence
Carcinoma, Ovarian Epithelial
Cell Proliferation - drug effects
Cell Survival - drug effects
Cell Survival - genetics
Chemoresistance
Chimera
Drug Resistance, Neoplasm - genetics
Female
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs - genetics
MicroRNAs - metabolism
MiRNA
Molecular Sequence Data
Mucin-1 - chemistry
Mucin-1 - genetics
Neoplasms, Glandular and Epithelial - drug therapy
Neoplasms, Glandular and Epithelial - genetics
Neoplasms, Glandular and Epithelial - metabolism
Ovarian cancer
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Paclitaxel
Paclitaxel - pharmacology
Signal Transduction
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Summary:The purpose of this study was to establish tumor tissue specific delivery of let-7i miRNA to reverse paclitaxel-induced chemoresistance. A chimera that combines MUC1 aptamer and let-7i miRNA was tested in OVCAR-3 ovarian cancer cells. Results demonstrated that the chimera can specifically be delivered into OVCAR-3 cells and the released let-7i significantly sensitized the role of paclitaxel in inhibiting cell proliferation, inducing cell apoptosis, and decreasing long-term cell survival. The chimera achieved reversal of chemoresistance through downregulation of cyclin D1, cyclin D2, Dicer 1, and PGRMC1 expressions. Our study indicated that this MUC1/let-7i chimera can specifically reverse chemoresistance to paclitaxel.
ISSN:0735-7907
1532-4192
DOI:10.3109/07357907.2012.707265