Downregulation of osteopontin enhances the sensitivity of glioma U251 cells to temozolomide and cisplatin by targeting the NF-κB/Bcl‑2 pathway

Qian,Chunfa; Li,Ping; Yan,Wei; Shi,Lei; Zhang,Junxia; Wang,Yingyi; Liu,Hongyi; You,Yongping

doi:10.3892/mmr.2014.2951

Downregulation of osteopontin enhances the sensitivity of glioma U251 cells to temozolomide and cisplatin by targeting the NF-κB/Bcl‑2 pathway

Authors:
- Chunfa Qian
- Ping Li
- Wei Yan
- Lei Shi
- Junxia Zhang
- Yingyi Wang
- Hongyi Liu
- Yongping You
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Affiliations: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Neurosurgery, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Neurosurgery, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Suzhou, Jiangsu 215300, P.R. China
Published online on: November 14, 2014 https://doi.org/10.3892/mmr.2014.2951
Pages: 1951-1955

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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.

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