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Ganoderma acid B induces Oct4 deSUMOylation and activates gastric cancer side population cells in G0 phase
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DOI   10.11656/j.issn.1672-1519.2019.04.21
Key Words   gastric cancer side population cells;small ubiquitin-like modifier;eight binding transcription factor 4;cisplatin;ganoderma acid B
Author NameAffiliationE-mail
CHENG Ruizhen Department of Pharmacy, Tianjin Binhai New Area Hospital of Traditional Chinese Medicine, Tianjin 300450, China  
ZHANG Chunyan Department of Pharmacy, Tianjin Binhai New Area Hospital of Traditional Chinese Medicine, Tianjin 300450, China  
LIU Fengting The College of Clinical Medicine of Tianjin Medical University, Tianjin 300070, China  
LI Rui Department of Pharmacy, Tianjin Binhai New Area Hospital of Traditional Chinese Medicine, Tianjin 300450, China  
WU Wenjing Department of Pharmacy, Tianjin Binhai New Area Hospital of Traditional Chinese Medicine, Tianjin 300450, China  
LI Yanxia The Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin 300450, China  
MA Xiaofang The Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin 300450, China  
LI Lili The College of Clinical Medicine of Tianjin Medical University, Tianjin 300070, China
Department of Bone and Soft Tissue Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of"Cancer Prevention and Therapy"of Tianjin, Tianjin Clinical Research Center for Malignant Tumor, Tianjin 300060, China 
 
LIU Xiaozhi The Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin 300450, China lxz7997@126.com 
Abstract
    [Objective] To study the activation effect of Ganoderma acid B (GAB) on gastric cancer side population cells in resting stage from the perspective of protein SUMOylation,and to provide a new strategy for the targeted therapy of gastric cancer side population cells.[Methods] Flow cytometry was used to isolate the SGC-7901 gastric cancer side population cells,and then treated with the active ingredient of traditional Chinese medicine,Ganoderma acid B (GAB) with final concentration of 10 μmol/L for 96 h. The diameter of cell clone was plotted at different time points. The change of cell cycle of gastric cancer side population cells was detected by flow cytometry technique. The expression level of small ubiquitin-like modifier (SUMO)-1,eight octamer binding transcription factors 4 (Oct4),Cyclin D1,Cyclin E1,Cyclin A2 and Cyclin B1 protein was detected by Western Blot assay. The median lethal dose (IC50) of cisplatin on gastric cancer side population cells was detected by MTT assay.[Results] The growth rate of gastric cancer side population cell clone balls in GAB group was significantly slower than the control group. The CD133+ gastric cancer side population cells in control group mainly in G0/G1 phase,and the GAB group cells mainly in G2/M phase. Compared with the control group,the expression level of Oct4,SUMO-1 and Cyclin D1 proteins was significantly decreased,but the level of Cyclin E1,Cyclin A2 and Cyclin B1 proteins was increased in GAB group (P<0.05). GAB induced IC50 from 69.84 g/mL down to 35.67 g/mL in gastric cancer side population cells to cisplatin.[Conclusion] GAB can activate resting gastric cancer side population cells by inducing Oct4 deSUMOylation,and increase their sensitivity to cisplatin.

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