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Mol. Hum. Reprod. Advance Access published online on February 8, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gah250
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received October 12, 2005
Revised November 18, 2005
Accepted November 22, 2005

Article

IFN{gamma} pretreatment sensitizes human choriocarcinoma cells to etoposide-induced apoptosis

Quan-Hong Sun 1, Jing-Pian Peng 1 *, and Hong-Fei Xia 1

1 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

* To whom correspondence should be addressed.
Jing-Pian Peng, E-mail: pengjp{at}ioz.ac.cn


  Abstract

Choriocarcinoma is a malignant trophoblast-derived tumour, which can arise in any type of gestation. Cell proliferation assays showed that interferon {gamma} (IFN{gamma}) alone significantly inhibited proliferation of choriocarcinoma JAR and JEG-3 cells. TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL) assays and Hoechst staining indicated that IFN{gamma} alone could not induce apoptosis of JAR and JEG-3 cells, but IFN{gamma} could enhance the sensitivity of JAR cells to etoposide-induced apoptosis. RT-PCR and western blotting were performed to detect expression of apoptosis-related molecules IFN{gamma}R, interferon regulatory factor-1 (IRF-1), p53 and pro-caspase 3. In JAR cells, etoposide increased expression of the proteins including IFN{gamma}R, p53 and pro-caspase 3 as well as IRF-1 mRNA and IFN{gamma}-pretreatment apparently promoted up-regulation of these molecules expression. In addition, the responses of IRF-1, p53 and pro-caspase 3 expression to IFN{gamma} pretreatment were dose dependent. IRF-1 knock down assays demonstrated that IRF-1 directly mediated IFN{gamma} pretreatment enhanced sensitivity of JAR cells to etoposide-induced apoptosis and that pro-caspase 3 was one of the target genes of IRF-1.

Keywords: apoptosis/IFN{gamma}/IRF-1/P53/pro-caspase 3.
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