title: Poly (I:C) transfection induces mitochondrial-mediated apoptosis in cervical cancer.
abstract: Polyinosinic acid:polycytidylic acid, known as poly (I:C), is an analogue of double‑stranded RNA, which exhibits direct antitumor effects against several types of cancer. The present study aimed to evaluate the role of poly (I:C) in the apoptosis of cervical cancer cells. The HeLa human cervical cancer cell line was used in the present study, and cell apoptosis was determined following poly (I:C) transfection. Furthermore, the mRNA levels of interferon (IFN)‑β, the production of reactive oxygen species (ROS), DNA damage, mitochondrial membrane potential (∆Ψm) and the release of cytochrome c, as well as caspase activation, were determined. The effect of IFN‑β on poly (I:C) transfection‑mediated apoptosis was also examined by IFN‑β knockdown. The results showed that poly (I:C) transfection markedly induced HeLa apoptosis, increased the protein levels of pro‑apoptotic B cell lymphoma‑2 (Bcl‑2)‑associated X protein (Bax) and BH3 interacting‑domain death agonist (Bid), and suppressed the protein expression levels of anti‑apoptotic Bcl‑2 and Survivin. However, poly (I:C) transfection increased the mRNA levels of IFN‑β, induced ROS production and increased the levels of phosphorylated γH2A.X, an indicator of DNA damage. In addition, poly (I:C) transfection decreased ∆Ψm, triggered the release of cytochrome c from the mitochondria to the cytosol, and induced caspase‑9 and ‑3 activation. IFN‑β knockdown decreased the poly (I:C)‑induced production of ROS and DNA damage, restored ∆Ψm and cytochrome c release, and suppressed caspase‑9 and ‑3 activation, thereby suppressing poly (I:C)‑mediated apoptosis in the HeLa cells. Together, the results of the present study demonstrated that poly (I:C) transfection induced IFN‑β, contributing to ROS production, DNA damage, and caspase‑9 and ‑3 activation in the HeLa cervical cancer cell line, leading to mitochondrial‑mediated apoptosis.
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors: Hui
authors: H
authors: Chen
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors: Dong-Liang
authors: DL
authors: Wang
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors: Yu-Ling
authors: YL
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011070:Poly I-C / Q000235:genetics / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053453:Caspase 9; D011070:Poly I-C