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Journal of Ovarian Research

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Open Access 01-12-2013 | Research

Antisense oligonucleotide suppression of human IGF-1R inhibits the growth and survival of in vitro cultured epithelial ovarian cancer cells

Authors: Jie Tang, Junjun Li, Guqing Zeng, Yanxiang Tang, Wenfang Tian, Jie He, J Philippe York, Xuefeng Xia

Published in: Journal of Ovarian Research | Issue 1/2013

Abstract

Background

Preclinical evaluation of the anti-neoplastic activity of antisense oligonucleotide (AS) suppression of human insulin-like growth factor I receptor (IGF-IR) in human epithelial ovarian cancer (EOC).

Methods

Ovarian cancer cells from 36 patients with EOC were investigated under serum-free tissue culture conditions. IGF-I production was evaluated by standard ELISA. IGF-IR and phosphorylated IRS-1, AKT, and MAP kinase expression and protein levels were evaluated by immunohistochemistry and Western blotting. Cancer cell growth and proliferation assays were performed in triplicates using MTT assay. Apoptosis was evaluated by TUNNEL assay.

Results

All ovarian cancer tissue samples tested produced IGF-I and expressed IGF-IR, supporting the existence of an autocrine loop. Treatment of primary ovarian cancer cell lines with an IGF-1R AS inhibited growth and proliferation and decreased clonogenicity in soft agar assay. AS treatment was demonstrated to inhibit the expression of IGF-1R and decrease the concentration of phosphorylated IRS-1, AKT, and MAP kinase signaling protein downstream of the IGF-IR. We also observed that the IGF-1R AS sensitized cancer cell lines to cisplatin in vitro through the PI3K pathway.

Conclusions

IGF-IR enhances the proliferation and tumorigenicity of human ovarian cancer cells and inhibition of IGF-IR by AS oligonucleotide treatment potentiates the activity of cisplatin in vitro. Therefore, IGF-1R is a potential molecular target in ovarian cancer.

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Title: Antisense oligonucleotide suppression of human IGF-1R inhibits the growth and survival of in vitro cultured epithelial ovarian cancer cells
Authors: Jie Tang
Junjun Li
Guqing Zeng
Yanxiang Tang
Wenfang Tian
Jie He
J Philippe York
Xuefeng Xia
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/1757-2215-6-71

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Antisense oligonucleotide suppression of human IGF-1R inhibits the growth and survival of in vitro cultured epithelial ovarian cancer cells

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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