[Effect and mechanism of tigecycline on proliferation of liver tumor cells in mouse model].

To analyze the effect and mechanisms of tigecycline on the proliferation of liver cancer cells in mouse model. Human hepatocellular carcinoma G2 (HepG2), human hepatocellular carcinoma 7 (Huh7), human hepatocellular carcinoma 3B (Hep3B) and Mahler's human hepatocellular carcinoma 97 high metastatic (MHCC97H) were divided into 6 groups respectively: group T0 (without tigecycline), group T1 (1.25 μmol/L tigecycline), group T2 (2.50 μmol/L tigecycline), group T3 (5.00 μmol/L tigecycline), group T4 (10.00 μmol/L tigecycline), and group T5 (20.00 μmol/L tigecycline). The proliferation capabilities of each group were compared after 48 hours of treatment (cell survival rate, the experiment was repeated 3 times). Based on the results of the effect of tigecycline on the proliferation ability of liver tumor cells, the mRNA and protein levels of ferroptosis-related genes [Acyl-CoA synthetase long chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and solute vector family member 11 (SLC7A11) ] in HepG2 and Hep3B cells in groups T0, T2 and T3 were detected (the experiment was repeated 3 times). Based on the results of the effects of tigecycline on the genes and protein levels of ACSL4, GPX4, and SLC7A11 in HepG2 and Hep3B, HepG2 and Hep3B cells were divided into 4 groups respectively: group T0, group T3, group T3F [5.00 μmol/L tigecycline combined with 10.00 μmol/L Ferrostatin-1 (Fer-1)] and group T3P [5.00 μmol/L tigecycline combined with 10.00 μmol/L ACSL4 specific inhibitor (PRGL493)], to compare the ACSL4 protein levels and cell proliferation abilities among different groups (cell survival rate, the experiment was repeated 3 times). HepG2 or Hep3B cell suspensions were subcutaneously injected into BALB/c nude mice to construct the subcutaneous tumor-bearing model of liver tumors in nude mice. On the 6th day, the mice were randomly divided into 3 groups (5 mice in each group for the HepG2 and Hep3B cell liver tumor nude mouse models): group N (no treatment), group TIG (treated with 100 mg/kg tigecycline), and group TP (treated with 100 mg/kg tigecycline combined with 0.5 mg/kg PRGL493). The effects of tigecycline on the proliferation of liver tumor cells in vivo and the ACSL4 protein in tumor tissues were detected, and the mechanism by which tigecycline inhibits the proliferation of liver tumor cells was analyzed. The survival rates of HepG2, Huh7, Hep3B, and MHCC97H cells in T1, T2, T3, T4, and T5 groups were all lower than that of T0 group (all <0.05); in both HepG2 and Hep3B cells, there was no statistically significant difference in the mRNA levels of ACSL4, GPX4, and SLC7A11, or in the protein levels of GPX4 and SLC7A11 between the T3 and T0 groups (all >0.05). However, the ACSL4 protein levels of HepG2 and Hep3B cells in T3 group were all higher than that of T0 group (all <0.05). The ACSL4 protein levels of HepG2 and Hep3B cells in T3F and T3P groups were lower than that of T3 group (all <0.05), and the cell survival rates of HepG2 and Hep3B cells in T3F and T3P groups were higher than that of T3 group(all <0.05). The tumor volumes of nude mouse subcutaneous tumor models in TIG group on the 21st day were lower than that of N group(all <0.05). The tumor volumes of nude mouse subcutaneous tumor models in TP group were higher than that of TIG group (all <0.05). Tigecycline inhibits the proliferation of liver cancer cells, and its mechanism may be related to promoting ACSL4-mediated ferroptosis.