Anti-tumor efficacy of Calculus bovis: Suppressing liver cancer by targeting tumor-associated macrophages

Abstract

Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies, liver cancer remains the fourth leading cause of cancer-related mortality worldwide. Tumor relapse, resistance to current anti-cancer drugs, metastasis, and organ toxicity are the major challenges that prevent considerable improvements in patient survival and quality of life. Calculus bovis (CB), an ancient Chinese medicinal drug, has been used to treat various pathologies, including stroke, convulsion, epilepsy, pain, and cancer. In this editorial, we discuss the research findings recently published by Huang et al on the therapeutic effects of CB in inhibiting the development of liver cancer. Utilizing the comprehensive transcriptomic analyses, in vitro experiments, and in vivo studies, the authors demonstrated that CB treatment inhibits the tumor-promoting M2 phenotype of tumor-associated macrophages via downregulating Wnt pathway. While multiple studies have been performed to explore the molecular mechanisms regulated by CB, this study uniquely shows its role in modulating the M2 phenotype of macrophages present within the tumor microenvironment. This study opens new avenues of future investigations aimed at investigating this drug’s efficacy in various mouse models including the effects of combination therapy, and against drug-resistant tumors.

Keywords: Calculus bovis; Liver cancer; M2-like tumor associated macrophages; Wnt/β-catenin pathway; Tumor environment

Core Tip: Calculus bovis, a traditional animal drug used in China, has been recognized for its therapeutic effects across various organ systems, including the central nervous, cardiovascular, respiratory, and digestive systems. Recent studies have also suggested its anti-tumor potential. While previous studies have explored the mechanisms of action of its active compounds, this study provides novel insights into its anti-tumor potential using a liver cancer xenograft model. M2 macrophages are associated with tumor progression because they promote tumor growth, angiogenesis, and metastasis while inhibiting effective anti-tumor immune responses. This study, for the first time, demonstrates that Calculus bovis modulates the tumor environment by governing M2-tumor-associated macrophages in a Wnt pathway-dependent manner, thereby suppressing tumor growth.