PMID- 26868822 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181113 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 414 IP - 1-2 DP - 2016 Mar TI - Induction of hypoxia-inducible factor-1alpha by BDNF protects retinoblastoma cells against chemotherapy-induced apoptosis. PG - 77-84 LID - 10.1007/s11010-016-2660-y [doi] AB - Alternations of environment signals such as neurotrophins may be the basis for malignant transformation of retinoblastoma (Rb), the most common primary intraocular malignancy in children. The aim of this study is to investigate the ability of brain-derived neurotrophic factor (BDNF) to decrease the chemosensitivity of Rb cells to the common chemotherapeutic agents and to explore the role of hypoxia-inducible factor-1alpha (HIF-1alpha) in such cellular process. The results showed that BDNF could induce higher expression of HIF-1alpha via activation of TrkB in human Y-79 retinoblastoma cells, which consequently contributed to its effect against chemotherapeutic agent-induced cytotoxicity and cell apoptosis. However, this protective effect could be potently reversed by knockdown of HIF-1alpha. Furthermore, BDNF strikingly prevented chemotherapeutic agent-induced alternations of apoptosis-related molecules, which could also be attenuated by silencing HIF-1alpha. Therefore, our findings demonstrated that BDNF could contribute to chemoresistance of Rb via modulation of HIF-1alpha expression, indicating that targeting at the BDNF-TrkB/HIF-1alpha signaling pathway might be a promising strategy for the treatment of retinoblastoma in the future. FAU - Gao, Yu AU - Gao Y AD - Department of Ophthalmology, No. 411 Hospital of CPLA, Shanghai, 200081, China. FAU - Jing, Ming AU - Jing M AD - Department of Ophthalmology, No. 411 Hospital of CPLA, Shanghai, 200081, China. FAU - Ge, Rongrong AU - Ge R AD - Department of Ophthalmology, No. 411 Hospital of CPLA, Shanghai, 200081, China. FAU - Lang, Lili AU - Lang L AD - Department of Ophthalmology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200081, China. lililang001@outlook.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160211 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Antineoplastic Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Membrane Glycoproteins) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (tropomyosin-related kinase-B, human) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/*drug effects MH - Brain-Derived Neurotrophic Factor/*physiology MH - Cell Line, Tumor MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis MH - Membrane Glycoproteins/metabolism MH - Protein-Tyrosine Kinases/metabolism MH - Receptor, trkB MH - Retinoblastoma/*pathology OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Chemotherapy resistance OT - Hypoxia-inducible factor-1alpha OT - Retinoblastoma EDAT- 2016/02/13 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/02/13 06:00 PHST- 2015/11/09 00:00 [received] PHST- 2016/02/03 00:00 [accepted] PHST- 2016/02/13 06:00 [entrez] PHST- 2016/02/13 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - 10.1007/s11010-016-2660-y [pii] AID - 10.1007/s11010-016-2660-y [doi] PST - ppublish SO - Mol Cell Biochem. 2016 Mar;414(1-2):77-84. doi: 10.1007/s11010-016-2660-y. Epub 2016 Feb 11.