Open AccessRespiratory chain complex I is related to oxidative phosphorylation in gastric cancer stem cells
Author(s) -
Changhong Peng,
Weibiao Kang,
Yunsong Li
Publication year - 2022
Publication title -
stemedicine
Language(s) - English
Resource type - Journals
ISSN - 2705-1188
DOI - 10.37175/stemedicine.v3i2.123
Subject(s) - phenformin , oxidative phosphorylation , cancer stem cell , cd44 , mitochondrial respiratory chain , cancer research , cancer cell , phosphorylation , respiratory chain , lgr5 , metastasis , biology , chemistry , cancer , stem cell , mitochondrion , microbiology and biotechnology , cell , endocrinology , biochemistry , metformin , insulin , genetics
Background: Cancer stem cells (CSCs) are the main cause of resistance to anti-cancer drug therapy and distant metastasis of tumors, including gastric cancer. The metabolism of CSCs is an important factor in the maintenance of its stemness. This study is intended to explore the role of oxidative phosphorylation in gastric CSCs.
Methods: EpCAM+CD44+ gastric CSCs were sorted from the SGC-7901 cell line. The oxidative phosphorylation and glycolysis were determined by Seahorse experiment, and the oxygen consumption of cells was determined by Clark’s oxygen electrodes. Gene expression and protein levels of mitochondrial proteins belonging to five respiratory chain complexes were checked. Phenformin and siRNA-NDUFB8 were used to inhibit respiratory chain complex I to explore the biological effect of enhanced oxidation phosphorylation in gastric CSCs. Cell migration capacity, proliferation ability, and vascular endothelial growth factor (VEGF) levels were also evaluated.
Results: Compared with control cells, the oxidation phosphorylation in mitochondria increased in EpCAM+CD44+ gastric CSCs, although the respiration level remained the same, and no significant changes were observed in glycolysis. Moreover, mRNA and protein expression levels of NDUFB8 in complex I were significantly increased. However, oxidative phosphorylation decreased in EpCAM+CD44+ cells after the treatment of phenformin and siRNA-NDUFB8 compared to the untreated cells. siRNA for NDFUB8 and phenformin inhibition also decreased the ability of cell migration, cell proliferation, as well as the VEGF secretion of gastric CSCs.
Conclusion: These results suggest that the increased oxidative phosphorylation was related to respiratory chain complex I and NDUFB8 in gastric CSCs.