title: IL-27 suppresses SKOV3 cells proliferation by enhancing STAT3 and inhibiting the Akt signal pathway.
abstract: Ovarian cancer continues to be the most lethal gynecologic malignancy worldwide. IL-27 is a novel member of the IL-12 cytokine family. The aim of this study was to investigate the effects of IL-27 on the ovarian cystadenocarcinoma cell line SKOV3 and determine possible mechanisms underlying its effect. We stably transfected an IL-27 plasmid, empty vector, IL-27 shRNA or negative control into SKOV3 cells. Cell proliferative activity was evaluated using a WST-1 cell proliferation assay kit. Cell viability was quantified by measurements of lactate dehydrogenase release. The mRNA levels of nine genes were tested by q-PCR. Western blotting was used to verify apoptosis and signal pathways. We found that the IL-27 plasmid significantly enhanced cytotoxicity and inhibited the proliferation of SKOV3 cells. Caspase-3 protein was augmented by IL-27 plasmid and abated by IL-27 shRNA. The incremental expression of IL-27 activated the STAT3 pathway and attenuated the Akt pathway. The over-expression of IL-27 could significantly upregulate a series of antitumor cytokines including IL-6, IL-12 and interferon-γ and down-regulate protumor factors such as TLR4 and NF-κB1. Our data show that IL-27 has direct antitumor capacity in ovarian cancer cells via enhancing apoptosis by inducing the STAT3 pathway and restraining the Akt pathway. Précis: IL-27 enhanced the cytotoxicity and suppressed the proliferation of ovarian cancer cells by activating STAT3 and inhibiting the Akt signal pathway. IL-27 plays an important role in antitumor activity against epithelial ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: zhanglin@scu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, China. Electronic address: qmrjzz@126.com.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Xi
mesh_terms: D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D003536:Cystadenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D007378:Interleukins; C464565:MYDGF protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Cytokine; IL-27; Ovarian cancer; Signal pathway