Feature Reports:Hepatocellular Carcinoma

Effects of sauchinone regulating KLF5⁃EphA2 pathway on the growth and immune escape of hepatocellular carcinoma cells

  • Shan WANG ,
  • Jinliang WAN ,
  • Zhonghua ZHAO ,
  • Jing YANG ,
  • Jie ZHAO ,
  • Yanzhang. HAO
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  • Department of Oncology,Affiliated Hospital of Binzhou Medical College,Binzhou 256603,Shandong,China

Received date: 2025-02-08

  Online published: 2025-05-21

Abstract

Objective To investigate the effects of sauchinone (Sch) on the growth and immune escape of liver cancer cells by regulating the Krüppel like factor 5 (KLF5)-erythropoietin-producing hepatocellular receptor A2 (EphA2) pathway. Methods Huh-7 cells were grouped into liver cancer group, Sch low, medium, and high-dose groups (Sch-L group, Sch-M group, Sch-H group), Sch-H + KLF5 activator negative control group (OE-NC), and Sch-H + KLF5 activator (OE-KLF5) group. 5-bromo-2-deoxyuracil (EdU) staining, CCK-8, scratch assay, and Transwll were used to detect the proliferation, migration, and invasion of Huh-7 cells, respectively. Western blot was applied to detect proliferative cell nuclear antigen (PCNA), migration invasion enhancer(MIEN1), matrix metalloproteinase-2 (MMP-2), programmed death receptor ligand 1 (PD-L1), KLF5, and EphA2 proteins in Huh-7 cells. The Huh-7 cells in above 6 groups were co cultured with activated CD8+ T cells in a 96 well plate and named as liver cancer co culture group, Sch-L co culture group, Sch-M co culture group, Sch-H co culture group, Sch-H + OE-NC co culture group, and Sch-H + OE-KLF5 co culture group. The killing rate of CD8+T cells in the co culture system and the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) in the supernatant were detected. Results Compared with the liver cancer group, the EdU positive rate, OD450 value, cell invasion number, and PCNA, MIEN1, MMP-2, PD-L1, KLF5, and EphA2 proteins in the Sch-L, Sch-M, and Sch-H groups reduced, the migration distance shorten (P < 0.05). Compared with the Sch-H group and Sch-H + OE-NC group, the EdU positive rate, OD450 value, cell invasion number, and PCNA, MIEN1, MMP-2, PD-L1, KLF5, and EphA2 proteins in the Sch-H + OE-KLF5 group increased, the migration distance prolonged (P < 0.05). Compared with the liver cancer co culture group, the killing rate of CD8+T cells on Huh-7 cells and the levels of IFN-γ, TNF-α, and IL-4 in the supernatant in the Sch-L co culture group, Sch-M co culture group, and Sch-H co culture group increased (P < 0.05). Compared with the Sch-H co culture group and the Sch-H + OE-NC co culture group, the killing rate of CD8+ T cells on Huh-7 cells and the levels of IFN-γ, TNF-α, and IL-4 in the supernatant in the Sch-H + OE-KLF5 co culture group decreased (P < 0.05). Conclusion Sch may inhibit growth and immune escape of liver cancer cells by inhibiting the KLF5-EphA2 pathway.

Cite this article

Shan WANG , Jinliang WAN , Zhonghua ZHAO , Jing YANG , Jie ZHAO , Yanzhang. HAO . Effects of sauchinone regulating KLF5⁃EphA2 pathway on the growth and immune escape of hepatocellular carcinoma cells[J]. The Journal of Practical Medicine, 2025 , 41(10) : 1480 -1486 . DOI: 10.3969/j.issn.1006-5725.2025.10.008

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