title: Downregulation of osteopontin enhances the sensitivity of glioma U251 cells to temozolomide and cisplatin by targeting the NF-κB/Bcl‑2 pathway.
abstract: Glioma is resistant to the apoptotic effects of chemotherapy and the mechanism underlying its chemoresistance is not currently understood. In a previous study, we reported that osteopontin (OPN) was overexpressed in glioma tissues and had an important anti‑apoptotic effect. Furthermore, overexpression of OPN was observed following chemotherapy. To elucidate whether OPN plays a role in chemotherapy resistance and to investigate its downstream signaling pathway, this study used small interfering RNA (siRNA) to silence the expression of OPN in U251 human neuronal glioma astrocytoma cells. OPN downregulation in U251 cells enhanced the apoptotic effects induced by temozolomide (TMZ) and cisplatin (DDP). Furthermore, OPN siRNA suppressed the nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) activation and B cell lymphoma 2 (Bcl‑2) expression that was induced by chemotherapy. Taken together, these results demonstrated that the expression levels of OPN are involved in glioma chemoresistance. Knockdown of OPN through siRNA enhanced the effects of TMZ and DDP chemotherapy by targeting the NF‑κB/Bcl‑2 pathway.
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Chunfa
authors.initials: C
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Suzhou, Jiangsu 215300, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D000077204:Temozolomide
chemical_list: D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D053495:Osteopontin; D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide