Ethyl pyruvate inhibits glioblastoma cells migration and invasion through modulation of NF-κB and ERK-mediated EMT

Qing Huang; Yongming Fu; Shan Zhang; Youxiang Zhang; Simin Chen; Zuping Zhang

doi:10.7717/peerj.9559

Ethyl pyruvate inhibits glioblastoma cells migration and invasion through modulation of NF-κB and ERK-mediated EMT

PeerJ. 2020 Jul 21:8:e9559. doi: 10.7717/peerj.9559. eCollection 2020.

Authors

Qing Huang¹, Yongming Fu², Shan Zhang¹, Youxiang Zhang¹, Simin Chen¹, Zuping Zhang¹

Affiliations

¹ Department of Pathogen Biology, School of Basic Medicine, Central South University, Changsha, China.
² Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China.

Abstract

Background: Glioblastoma is a grade IV glioma with the highest degree of malignancy and extremely high incidence. Because of the poor therapeutic effect of surgery and radiochemotherapy, glioblastoma has a high recurrence rate and lethality, and is one of the most challenging tumors in the field of oncology. Ethyl pyruvate (EP), a stable lipophilic pyruvic acid derivative, has anti-inflammatory, antioxidant, immunomodulatory and other cellular protective effects. It has been reported that EP has potent anti-tumor effects on many types of tumors, including pancreatic cancer, prostate cancer, liver cancer, gastric cancer. However, whether EP has anti-tumor effect on glioblastoma or not is still unclear.

Methods: Glioblastoma U87 and U251 cells were treated with different concentrations of EP for 24 h or 48 h. CCK8 assay and Colony-Formation assay were performed to test the viability and proliferation. Wound-healing assay and Transwell assay were carried out to measure cell invasion and migration. Western blot was not only used to detect the protein expression of epithelial-mesenchymal transition (EMT)-related molecules, but also to detect the expression and activation levels of NF-κB (p65) and Extracellular Signal Regulated Kinase (ERK).

Results: In glioblastoma U87 and U251 cells treated with EP, the viability, proliferation, migration, invasion abilities were inhibited in a dose-dependent manner. EP inhibited EMT and the activation of NF-κB (p65) and ERK. With NF-κB (p65) and ERK activated, EMT, migration and invasion of U87 and U251 cells were promoted. However the activation of NF-κB (p65) and ERK were decreased, EMT, migration and invasion abilities were inhibited in U87 and U251 cells treated with EP.

Conclusion: EP inhibits glioblastoma cells migration and invasion by blocking NF-κB and ERK-mediated EMT.

Keywords: EMT (epithelial–mesenchymal transition); ERK; Ethyl pyruvate; Glioblastoma; Invasion; Migration; NF-κB.

Grants and funding

This work was supported by a grant from the National Natural Science Foundation of China (NO. 81372183). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.