IFNgamma pretreatment sensitizes human choriocarcinoma cells to etoposide-induced apoptosis.
Choriocarcinoma is a malignant trophoblast-derived tumour, which can arise in any type of gestation. Cell proliferation assays showed that interferon gamma (IFNgamma) 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 IFNgamma alone could not induce apoptosis of JAR and JEG-3 cells, but IFNgamma 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 IFNgammaR, interferon regulatory factor-1 (IRF-1), p53 and pro-caspase 3. In JAR cells, etoposide increased expression of the proteins including IFNgammaR, p53 and pro-caspase 3 as well as IRF-1 mRNA and IFNgamma-pretreatment apparently promoted up-regulation of these molecules expression. In addition, the responses of IRF-1, p53 and pro-caspase 3 expression to IFNgamma pretreatment were dose dependent. IRF-1 knock down assays demonstrated that IRF-1 directly mediated IFNgamma pretreatment enhanced sensitivity of JAR cells to etoposide-induced apoptosis and that pro-caspase 3 was one of the target genes of IRF-1.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Quan-Hong
QH
Sun
Jing-Pian
JP
Peng
Hong-Fei
HF
Xia
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D005047:Etoposide; D007371:Interferon-gamma