Apatinib reduces liver cancer cell multidrug resistance by modulating NF-κB signaling pathway

Objectives: This investigation aimed to elucidate the inhibitory impact of apatinib on the multidrug resistance of liver cancer both in vivo and in vitro. Methods: To establish a Hep3B/5-Fu resistant cell line, 5-Fu concentrations were gradually increased in the culture media. Hep3B/5-Fu cells drug resistance and its alleviation by apatinib were confirmed via flow cytometry and Cell Counting Kit 8 (CCK8) test. Further, Nuclear factor kappa B (NF-kappa B) siRNA was transfected into Hep3B/5-Fu cells to assess alterations in the expression of multidrug resistance (MDR)-related genes and proteins. Nude mice were injected with Hep3B/5-Fu cells to establish subcutaneous xenograft tumors and then categorized into 8 treatment groups. The treatments included oxaliplatin, 5-Fu, and apatinib. In the tumor tissues, the expression of MDRrelated genes was elucidated via qRT-PCR, immunohistochemistry, and Western blot analyses. Results: The apatinibtreated mice indicated slower tumor growth with smaller size compared to the control group. Both the in vivo and in vitro investigations revealed that the apatinib-treated groups had reduced expression of MDR genes GST-pi, LRP, MDR1, and p-p65. Conclusions: Apatinib effectively suppresses MDR in human hepatic cancer cells by modulating the expression of genes related to MDR, potentially by suppressing the NF-kappa B signaling pathway.