Background: The molecular mechanisms involved in the development and metastasis of hepatocellular carcinoma (HCC) are complex. Molecule-targeted drugs are characterized by strong specificity and low toxicity, but the clinical research of these drugs still exhibits many difficulties, such as poor target specificity. With the in-depth study of the tumor immunological theory, therapies based on overcoming the tumor immune escape to produce a specific effective tumor immune response has gradually become a hot topic in tumor research. We hope that by studying the effects of liver-targeted drugs on the expression of immune-related proteins in hepatocellular carcinoma cells, we will find a potential link to further guide the clinical drug use.
Methods: Human hepatoma Hep3B cells were used to establish liver cancer xenografts by inoculating 40 BALB/c nude mice. The following five groups of mice (8 mice per group) were randomly set up: lenvatinib group, apatinib group, sorafenib group, regorafenib group, and dimethyl sulfoxide (DMSO) group. After treatment, we analyzed PD-L1 and B7-H3 mRNA using the real-time polymerase chain reaction (PCR) assay and assessed the PD-L1 and B7-H3 protein expression by Western immunoblotting.
Results: Real-time PCR results suggested that the mRNA expression of PD-L1 in the lenvatinib group was significantly higher than that in the control group, while its expression in the regorafenib group was significantly lower than that in the control group (both p < .05). Western immunoblotting results suggested that, compared with the control group, PD-L1 protein was increased in the lenvatinib group, while its expression in the regorafenib group was decreased.
Conclusion: Lenvatinib and regorafenib affected the expression of PD-L1 in the process of anti-HCC.
Keywords: B7-H3; Hepatocellular carcinoma; Immune checkpoint blockades; Liver targeted drugs; PD-L1.
Copyright © 2018. Published by Elsevier B.V.