Babaodan inhibits cell proliferation and metastasis and enhances anti-tumor effects of camrelizumab by inhibiting M2 phenotype macrophages in hepatocellular carcinoma

Abstract

Ethnopharmacological relevance: Babaodan (BBD) is a unique Chinese medication utilized in traditional Chinese medicine. It can eliminate toxins, induce diuresis, and eliminate yellowish hue. In addition to treating acute and chronic viral hepatitis, cholecystitis, cholangitis, and urinary tract infections, BBD has garnered popularity as a substitution treatment for several malignant cancers, particularly hepatocellular carcinoma (HCC).

Aim of the study: To elucidate the efficacy and mechanism of BBD alone and combined with camrelizumab (CLM) for treating HCC.

Methods: We investigated the effects of BBD on the HCC tumor microenvironment in vivo. Furthermore, we evaluated its effects on tumor growth and metastasis induced by M2 macrophages in vitro.

Results: In a mouse model of orthotopic HCC, BBD decreased tumor growth. Furthermore, it increased the M1/M2 macrophage ratio and CD8⁺ T-cell abundance in mice. In addition, BBD reversed HCC cell proliferation and metastasis induced by M2 macrophages, increased the anti-HCC effect of low-dose CLM, and attenuated organ damage induced by high-dose CLM. Lastly, BBD enhanced the efficacy of CLM via the PI3K/AKT/mTOR signaling pathway.

Conclusion: BBD increases the antitumor effect of CLM by modulating the tumor immune microenvironment and attenuating its the toxic side effects of CLM.

Keywords: Babaodan capsule (BBD); CD8+ T cell; Hepatocellular carcinoma(HCC); Macrophage.