Synergistic anti-tumor effect of donafenib combined with histone deacetylase inhibitor on hepatocarcinoma cell lines

DAI Ya-feng; LI Hui; WU Di; LI Xiao-ting; ZHANG Peng-jun; ZHU Xu

doi:10.3969/j.issn.1003-3734.2024.13.011

Abstract：Objective:To investigate the effect of donafenib combined with histone deacetylase inhibitor(HDACi)cambinol on the proliferation and apoptosis of hepatocellular carcinoma cells and the therapeutic efficacy of the combination on HuH-7 cell line xenografts in BALB/c-nude mice.Methods:HuH-7 and Hep3B 2.1-7 cell lines were treated with different concentrations of donafenib,cambinol and the combination of the two drugs.CCK-8 reagent was used to detect the OD value and then calculate the proliferation inhibition rate.Apoptosis and cell cycle were detected by flow cytometry.A xenograft model in BALB/c-nude mice was established to evaluate whether a synergistic effect exists for the combination of donafenib and cambinol in vivo experiments.Results:The proliferation of HuH-7 and Hep3B 2.1-7 cells was inhibited by donafenib or cambinol alone,and the ability to inhibit proliferation was significantly increased in the combination group(P<0.01).The combination index(CI)was less than 1 in both cell lines.Compared with the single drug groups,the combined drug group induced increased apoptosis.The proportion of cells in each cycle did not change significantly.The combination therapy group significantly inhibited the migration of liver cancer cells,and reduced the expression of ABCB1.Furthermore,the combined drug group synergistically suppressed the growth of xenograft tumors in BALB/c-nude mice with a Q value<1.15.Conclusion:The combination of donafenib and cambinol can inhibit the proliferation of tumor cells and synergistically suppress the growth of xenograft tumors in nude mice,which may be caused by the induction of apoptosis or related to ABCB1/MDR1/P-gp of the ATP binding cassette transporter superfamily.