Berberine in combination with anti-PD-L1 suppresses hepatocellular carcinoma progression and metastasis via Erk signaling pathway.

BACKGROUND

Berberine (BBR) is an isoquinoline alkaloid extracted from Huang Lian and other herbal medicines. It has been reported to play a crucial role in multiple metabolic diseases and cancers. Programmed cell death-1 (PD-L1) is known as the immune checkpoint; immunotherapy targeting PD1/PD-L1 axis can effectively block its pro-tumor activity. However, the effect of the combined use of BBR and anti-PD-L1 on hepatocellular carcinoma (HCC) has not been reported.

METHODS

Hep-3B and HCCLM3 cells were chosen as the experimental objects. To determine the potential anti-cancer activity of the combination of BBR and anti-PD-L1, we first treated v cells with BBR. The cell viability of Hep-3B and HCCLM3 with BBR treatment was measured by Cell Count Kit 8 assay. Cytometry by time-of-flight was performed to analyze tumor tissues after treatment with BBR and/or anti-PD-L1. Proliferation-, migration-, and invasion-related markers were measured by western blotting and immunohistochemistry.

RESULTS

The results showed that BBR significantly inhibited the proliferation of Hep-3B and HCCLM3.The combination treatment of BBR and anti-PD-L1 had a prominent inhibitory effect on HCC tumorigenesis. Cytometry by time-of-flight analysis indicated that BBR affects the immune subsets in the tumors. Besides, BBR and anti-PD-L1 inhibited the migration and invasion of HCC by inactivating the phosphorylation of Erk.

CONCLUSION

Our study proposed that the combination treatment of BBR and anti-PD-L1 markedly inhibited the tumorigenesis of HCC by Erk signaling pathway. We hope our research can provide a new strategy for the potential of BBR as a therapeutic agent in the treatment of HCC.