Blocking interleukin-6 signaling inhibits cell viability/proliferation, glycolysis, and colony forming activity of human medulloblastoma cells

Author: Chen, Xiang; Wei, Jia; Li, Chenglong; Pierson, Christopher R.; Finlay, Jonathan L.; Lin, Jiayuh

Description: Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) have tumor-promoting activity and are associated with poor survival outcomes in many cancers. Additionally, the IL-6/GP130/STAT3 axis has been widely studied due to its pivotal role in tumor development and maintenance in a number of tissue types, including the cerebellum. However, the connection between IL-6 signaling and medulloblastoma progression is largely unexplored. In the present study, we observed that IL-6 induced medulloblastoma cell viability, cell proliferation and glycolysis. Furthermore, it also upregulated the expression of phosphorylated STAT3, indicating that the IL-6/GP130/STAT3 pathway plays a central role in medulloblastoma. The FDA-approved drug bazedoxifene, a blocker of the formation of the hexameric IL-6/IL-6R/GP130 complex, was re-purposed in this study to inhibit the IL-6/GP130/STAT3 signaling pathway. Bazedoxifene not only inhibited IL-6 mediated cell viability and cell proliferation, and increased phosphorylated STAT3 expression, but it also decreased cell glycolysis, demonstrating a certain level of therapeutic efficacy in vitro. Collectively, our findings offer new insight into the molecular mechanism underlying the biological aggressiveness of medulloblastoma, the roles of IL-6 in these processes and a possible efficacious adjuvant therapy for medulloblastoma.

Subject headings: Cell Line; Tumor; Cell Proliferation; Cell Survival; Cerebellar Neoplasms; Glycolysis; Humans; Interleukin-6; Medulloblastoma; Signal Transduction; Cancer

Publication year: 2018

Journal or book title: International Journal of Oncology

Volume: 52

Issue: 2

Pages: 571-578

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Serial number: 3697

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