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생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma

  • Jae Kook Yang (Department of Internal Medicine, Soonchunhyang University College of Medicine Cheonan Hospital) ;
  • Junhyung Kim (Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University) ;
  • Young Hyeon Ahn (Department of Internal Medicine, Soonchunhyang University College of Medicine Cheonan Hospital) ;
  • Sang Ho Bae (Department of Surgery, Soonchunhyang University College of Medicine Cheonan Hospital) ;
  • Moo-Jun Baek (Department of Surgery, Soonchunhyang University College of Medicine Cheonan Hospital) ;
  • Sae Hwan Lee (Department of Internal Medicine, Soonchunhyang University College of Medicine Cheonan Hospital) ;
  • Jong-Seok Moon (Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University)
  • 투고 : 2024.05.10
  • 심사 : 2024.09.01
  • 발행 : 2024.10.31
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초록

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. HCC occurs people with chronic liver diseases. The purinergic receptor P2X 7 (P2RX7) is involved in tumor proliferation and growth. Also, P2RX7 is associated with tumor invasion and metastatic dissemination. High glucose utilization is important for the survival of various types of tumors. However, the role of P2RX7 in glucose metabolism and cellular survival of HCC remains unclear. Here, our results show that the gene and protein levels of P2RX7 were elevated in tumor cells of patients with HCC. The pharmacological inhibition of P2RX7 by A-804598, a selective P2RX7 antagonist, and genetic inhibition by P2RX7 knockdown suppressed the glycolytic activity by reduction of hexokinase 2 (HK2), a key enzyme of the glycolysis pathway, in human HCC cells. Also, both A-804598 treatment and P2RX7 knockdown induced cytotoxicity via inhibition of AKT activation which is critical for tumor cell survival in human HCC cells. Moreover, A-804598 treatment and P2RX7 knockdown increased cytotoxicity and caspase-3 activation in human HCC cells. These results suggest that inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human HCC.

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과제정보

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF- 2019M3E5D1A02069065 to J.K.Y and RS-2024-00353561 to J.-S.M.) and Soonchunhyang University Research Fund.

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