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Induction of hypoxia-inducible factor-1α by BDNF protects retinoblastoma cells against chemotherapy-induced apoptosis

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Abstract

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-1α (HIF-1α) in such cellular process. The results showed that BDNF could induce higher expression of HIF-1α 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-1α. Furthermore, BDNF strikingly prevented chemotherapeutic agent-induced alternations of apoptosis-related molecules, which could also be attenuated by silencing HIF-1α. Therefore, our findings demonstrated that BDNF could contribute to chemoresistance of Rb via modulation of HIF-1α expression, indicating that targeting at the BDNF-TrkB/HIF-1α signaling pathway might be a promising strategy for the treatment of retinoblastoma in the future.

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Acknowledgments

This work was supported by funds of Tongji University (2012KJ042), Shanghai Municipality Health and Family Planning Commission (201540304), and Hongkou District of Shanghai Municipality Health and Family Planning Commission (1402-11).

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Authors and Affiliations

  1. Department of Ophthalmology, No. 411 Hospital of CPLA, Shanghai, 200081, China

    Yu Gao, Ming Jing & Rongrong Ge

  2. Department of Ophthalmology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200081, China

    Lili Lang

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  1. Yu Gao
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  2. Ming Jing
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  3. Rongrong Ge
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  4. Lili Lang
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Correspondence to Lili Lang.

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Gao, Y., Jing, M., Ge, R. et al. Induction of hypoxia-inducible factor-1α by BDNF protects retinoblastoma cells against chemotherapy-induced apoptosis. Mol Cell Biochem 414, 77–84 (2016). https://doi.org/10.1007/s11010-016-2660-y

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  • DOI: https://doi.org/10.1007/s11010-016-2660-y

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