IMR Press / FBL / Volume 27 / Issue 9 / DOI: 10.31083/j.fbl2709262
Open Access Original Research
PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells
Show Less
1 Women's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, China
2 Department of Gynecology, The first Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, Zhejiang, China
3 Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, China
*Correspondence: lbwg@zju.edu.cn (Weiguo Lu)
These authors contributed equally.
Academic Editor: Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(9), 262; https://doi.org/10.31083/j.fbl2709262
Submitted: 8 May 2022 | Revised: 6 July 2022 | Accepted: 30 July 2022 | Published: 16 September 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Enhanced glycolysis occurs in most human cancer cells and is related to chemoresistance. However, detailed mechanisms remain vague. Methods: Using proteinomics analysis, we found that the glycolytic enzyme Phosphoglycerate mutase 1 (PGAM1) was highly expressed in the paclitaxel-resistant ovarian cancer cell line SKOV3-TR30, as compared to its parental cell line SKOV3. Cell Counting Kit-8 proliferation experiment, plasmids and siRNA transfection, pyruvic acid and lactic acid production detection, immunofluorescence staining of functional mitochondria and oxygen consumption rate and extracellular acidification rate measurement were uesd to assess the glycolytic metabolism and paclitaxel resistance in ovarian cancer cells. The expression and prognostic effect of PGAM1 in 180 ovarian cancer patients were analyzed. Results: SKOV3-TR30 cells display higher glycolytic flux and lower mitochondrial function than SKOV3 cells. Down-regulation of PGAM1 in SKOV3-TR30 cells resulted in decreased paclitaxel resistance. Up-regulation of PGAM1 in SKOV3 cells led to enhanced paclitaxel resistance. Analysis of the glycolytic flux revealed that PGAM1-mediated pyruvic acid or lactic acid production could modulate the capabilities of ovarian cancer cell resistance to paclitaxel. Our data also show high expression of PGAM1 as significantly correlated with reduced overall survival and reduced progression free survival in ovarian cancer patients. Conclusions: PGAM1 acts to promote paclitaxel resistance via pyruvic acid and/or lactate production in ovarian cancer cells. Inhibiting PGAM1 may provide a new approach to favorably alter paclitaxel resistance in ovarian cancer.

Keywords
Phosphoglycerate mutase 1
paclitaxel resistance
glycolysis
pyruvate
ovarian cancer cell
Figures
Fig. 1.
Funding
2017211914/ Medicine and Health Research Project of Zhejiang Province
2013KYA106/ The Research Project in Health Commission of Zhejiang Province
Y201328866/ The Research Project of Department of Education of Zhejiang Province
Share
Back to top