Apilimod enhances specific productivity in recombinant CHO cells through cell cycle arrest and mediation of autophagy.

Autor: Lu JT; School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, China.; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, Henan, China.; Henan Engineering Research Center for Biopharmaceutical Innovation, Xinxiang Medical University, Xinxiang, Henan, China., Xiao MK; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, Henan, China.; Henan Engineering Research Center for Biopharmaceutical Innovation, Xinxiang Medical University, Xinxiang, Henan, China.; School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China., Feng YY; School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, China.; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, Henan, China.; Henan Engineering Research Center for Biopharmaceutical Innovation, Xinxiang Medical University, Xinxiang, Henan, China., Wang XY; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, Henan, China.; Henan Engineering Research Center for Biopharmaceutical Innovation, Xinxiang Medical University, Xinxiang, Henan, China.; School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, China., Qiu LL; School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, China., Chai YR; Department of Histology and Embryology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China., Wang TY; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, Henan, China.; Henan Engineering Research Center for Biopharmaceutical Innovation, Xinxiang Medical University, Xinxiang, Henan, China.; School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, China., Jia YL; School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, China.; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, Henan, China.; Henan Engineering Research Center for Biopharmaceutical Innovation, Xinxiang Medical University, Xinxiang, Henan, China.
Jazyk: angličtina
Zdroj: Biotechnology journal [Biotechnol J] 2023 Feb; Vol. 18 (2), pp. e2200147. Date of Electronic Publication: 2022 Dec 14.
DOI: 10.1002/biot.202200147
Abstrakt: Chinese hamster ovary (CHO) cells are expected to acquire the ability to produce higher recombinant therapeutic protein levels using various strategies. Genetic engineering targeting the cell cycle and autophagy pathways in the regulation of cell death in CHO cell cultures has received attention for enhancing the production of therapeutic proteins. In this study, we examined the small-molecule compound apilimod, which was found to have a positive influence on recombinant protein expression in CHO cells. This was confirmed by selective blocking of the cell cycle at the G0/G1 phase. Apilimod treatment resulted in decreased expression of cyclin-dependent kinase 3 (CDK3) and Cyclin C and increased expression of cyclin-dependent kinase suppressor p27Kip1, which are critical regulators of G1 cell cycle progression and important targets controlling cell proliferation. Furthermore, total transcription factor EB (TFEB) was lower in apilimod-treated CHO cells than in control cells, resulting in decreased lysosome biogenesis and autophagy with apilimod treatment. These multiple effects demonstrate the potential of apilimod for development as a novel enhancer for the production of recombinant proteins in CHO cell engineering.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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