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Enhancement of recombinant human IL-24 (rhIL-24) protein production from site-specific integrated engineered CHO cells by sodium butyrate treatment | |
Hua, Jilei1; Xu, Hanli1; Zhang, Yao1,2; Ge, Jianlin1; Liu, Mengzhe1; Wang, Yuqi1; Wei, Yuexian1; Shi, Yinan1,3; Hou, LingLing1; Jiang, Hong1 | |
2022-10-25 | |
Source Publication | BIOPROCESS AND BIOSYSTEMS ENGINEERING
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ISSN | 1615-7591 |
Pages | 13 |
Abstract | Interleukin-24 (IL-24) has specific inhibitory effects on the proliferation of various tumor cells with almost no toxicity to normal cells. The antitumor activity of recombinant human IL-24 protein produced in mammalian cells is much higher than that of bacteria, but its expression level is extremely low. Sodium butyrate (NaBu) was utilized as a media additive to increase protein expression in Chinese hamster ovary cells. The site-specific integrated engineered cells FCHO/IL-24 were treated with NaBu under different culture conditions (10% and 0.5% serum adherent culture, 0.5% serum suspension culture). First, 3 days of 1 mmol/L NaBu treatment significantly increased rhIL-24 expression level in FCHO/IL-24 cells by 119.94 +/- 1.5% (**p < 0.01), 57.49 +/- 2.4% (**p < 0.01), and 20.17 +/- 3.03% (*p < 0.05) under the above culture conditions. Second, NaBu has a time- and dose-dependent inhibitory effect on FCHO/IL-24 proliferation and induces G0/G1 phase arrest. Under 10% and 0.5% serum adherent culture, G0/G1 phase cells were increased by 11.3 +/- 0.5% (**p < 0.01) and 15.0 +/- 2.6% (**p < 0.01), respectively. No induction of apoptosis was observed under a high dosage of NaBu treatment. These results suggest that NaBu increases rhIL-24 secretion via inhibiting cell cycle progression, thereby trapping cells in the highly productive G0/G1 phase. Finally, with increasing NaBu dose, glucose concentration increased (**p < 0.01) while lactic acid and ammonia concentrations reduced significantly (**p < 0.01) in 10% and 0.5% serum adherent culture supernatant. RNA-seq showed that NaBu treatment affected multiple tumor and immune-related pathways. In conclusion, NaBu treatment dramatically promoted rhIL-24 production in engineered FCHO/IL-24 cells by altering downstream pathways and inducing G0/G1 cell arrest with little effect on apoptosis. |
Keyword | rhIL-24 Serum-free culture Suspension culture CHO cells Sodium butyrate |
DOI | 10.1007/s00449-022-02801-0 |
Language | 英语 |
WOS Keyword | GENE-EXPRESSION ; CULTURE ; MDA-7/IL-24 ; APOPTOSIS ; TRANSCRIPTOME ; INCREASES ; AUTOPHAGY ; GROWTH ; MDA-7 ; PA |
Funding Project | Fundamental Research Funds for the Central Universities[2021RC207] ; Beijing Natural Science Foundation[7214242] |
WOS Research Area | Biotechnology & Applied Microbiology ; Engineering |
WOS Subject | Biotechnology & Applied Microbiology ; Engineering, Chemical |
Funding Organization | Fundamental Research Funds for the Central Universities ; Beijing Natural Science Foundation |
WOS ID | WOS:000871861800001 |
Publisher | SPRINGER |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ipe.ac.cn/handle/122111/55169 |
Collection | 中国科学院过程工程研究所 |
Corresponding Author | Hou, LingLing; Jiang, Hong |
Affiliation | 1.Beijing Jiaotong Univ, Coll Life Sci & Bioengn, 3 Shangyuancun, Beijing 100044, Peoples R China 2.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China 3.China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing 100700, Peoples R China |
Recommended Citation GB/T 7714 | Hua, Jilei,Xu, Hanli,Zhang, Yao,et al. Enhancement of recombinant human IL-24 (rhIL-24) protein production from site-specific integrated engineered CHO cells by sodium butyrate treatment[J]. BIOPROCESS AND BIOSYSTEMS ENGINEERING,2022:13. |
APA | Hua, Jilei.,Xu, Hanli.,Zhang, Yao.,Ge, Jianlin.,Liu, Mengzhe.,...&Jiang, Hong.(2022).Enhancement of recombinant human IL-24 (rhIL-24) protein production from site-specific integrated engineered CHO cells by sodium butyrate treatment.BIOPROCESS AND BIOSYSTEMS ENGINEERING,13. |
MLA | Hua, Jilei,et al."Enhancement of recombinant human IL-24 (rhIL-24) protein production from site-specific integrated engineered CHO cells by sodium butyrate treatment".BIOPROCESS AND BIOSYSTEMS ENGINEERING (2022):13. |
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