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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2019, Vol. 24 ›› Issue (10): 1134-1141.doi: 10.12092/j.issn.1009-2501.2019.10.008

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Effects of circadian clock gene Period2 on Warburg effect and metastasis in hepatocellular carcinoma cells

ZHAO Qiaosu1,YE Hua1,SUN Qinxue2   

  1. 1 Department of Gastroenterology,2 Department of Radiology,Ningbo Medical Center Li Huili Hospital,Ningbo 315000,Zhejiang,China
  • Received:2019-04-19 Revised:2019-06-03 Online:2019-10-26 Published:2019-10-28

Abstract:

AIM: To study the effects of circadian clock gene Period2 on Warburg effect and metastasis in hepatocellular carcinoma cells. METHODS: Real-time fluorescence quantitative PCR (RT-QPCR) was used to detect the expression of Period2 in tissues and 4 hepatocellular carcinoma cells,up-regulated the expression of Period2 in hepatocellular carcinoma cell line MHCC97L.silenced the expression of Period2 in hepatocellular carcinoma cell line HepG2.The glucose uptake level,lactic acid level,cell oxygen consumption level,cell viability,migration,and cell invasion were detected.Western-Blot was used to detect the expression of the key metabolic enzymes.RESULTS:The expression level of Period2 in MHCC97L was low,while HepG2 level was high.After Period2 silencing, the relative glucose uptake and lactate production of HepG2 cells were down-regulated compared with control group, and the oxygen consumption of HepG2 cells was increased compared with control,and the cell viability, migration and invasion ability were decreased.The expression level of key enzymes of glycometabolism was down-regulated.After overexpression of Period2,the glucose uptake level of MHCC97L cells was increased,the lactate production level was increased,the oxygen consumption was decreased compared with control, and the cell viability, migration and invasiveness were increased.The expression level of key enzymes of glucose metabolism was up-regulated.CONCLUSION: The clock gene Period2 is highly expressed in HCC, and its role is related to the promotion of Warburg effect and metastasis and invasion of HCC cells.

Key words: clock gene, cancer, Hepatocyte, Warburg effect, metastasis, invasion

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