Research Paper Volume 13, Issue 17 pp 21268—21282

Celecoxib reverses the glioblastoma chemo-resistance to temozolomide through mitochondrial metabolism

Delong Yin1, *, , Guoqing Jin2, *, , Hong He3, , Wei Zhou1, , Zhenbo Fan1, , Chen Gong4, , Jing Zhao4, , Huihua Xiong4, ,

  • 1 Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
  • 2 Department of Intensive Care Unit, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
  • 3 Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
  • 4 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
* Equal contribution

Received: May 2, 2021       Accepted: July 1, 2021       Published: September 8, 2021      

https://doi.org/10.18632/aging.203443
How to Cite

Copyright: © 2021 Delong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Temozolomide (TMZ) is used for the treatment of high-grade gliomas. Acquired chemoresistance is a serious limitation to the therapy with more than 90% of recurrent gliomas showing little response to a second line of chemotherapy. Therefore, it is necessary to explore an alternative strategy to enhance the sensitivity of glioblastoma (GBM) to TMZ in neuro-oncology. Celecoxib is well known and widely used in anti-inflammatory and analgesic. Cyclooxygenase-2 (COX-2) expression has been linked to the prognosis, angiogenesis, and radiation sensitivity of many malignancies such as primitive neuroectodermal tumor and advanced melanoma. The objective of this study was to explore the chemotherapy-sensitizing effect of celecoxib on TMZ in GBM cells and its potential mechanisms. From the study, we found that the combination therapy (TMZ 250uM+celecoxib 30uM) showed excellent inhibitory effect to the GBM, the LN229 and LN18, which were the TMZ resistant GBM cell lines. Our data suggest that the combination therapy may inhibits cell proliferation, increases apoptosis, and increases the autophagy on LN229 and LN18. The potential molecular mechanisms were related to mitochondrial metabolism and respiratory chain inhibition.

Abbreviations

TMZ: Temozolomide; GBM: Glioblastoma; COX-2: Cyclooxygenase-2; CVS: violet staining; OXPHOS: oxidative phosphorylation; mtDNA: mitochondrial DNA; ETC: electron transport chain; FDA: Drug Administration; TFAM: Mitochondrial transcription factor A; DMSO: dimethyl sulfoxide; CSC: cancer stem cells; ATCC: American Type Culture Collection.