Unlocking the potential of Calculus bovis: A breakthrough in liver cancer treatment via Wnt/β-catenin pathway modulation

Abstract

Liver cancer remains a significant global health challenge, characterized by high incidence and mortality rates. Despite advancements in medical treatments, the prognosis for liver cancer patients remains poor, highlighting the urgent need for novel therapeutic approaches. Traditional Chinese medicine (TCM), particularly Calculus bovis (CB), has shown promise in addressing this need due to its multi-target therapeutic mechanisms. CB refers to natural or synthetic gallstones, traditionally sourced from cattle, and used in TCM for their anti-inflammatory, detoxifying, and therapeutic properties. In modern practice, synthetic CB is often utilized to ensure consistent supply and safety. This article aims to discuss the findings of Huang et al, who investigated the anti-liver cancer properties of CB, focusing on its ability to inhibit M2 tumor-associated macrophage (TAM) polarization via modulation of the Wnt/β-catenin pathway. Huang et al employed a comprehensive approach integrating chemical analysis, animal model testing, and advanced bioinformatics. They identified active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms through network pharmacology, transcriptomics, and molecular docking studies. The study demonstrated that CB significantly inhibited liver tumor growth in vivo, as evidenced by reduced tumor size and weight in treated mice. Histological analyses confirmed signs of tumor regression. CB was found to modulate the tumor microenvironment by inhibiting the polarization of M2 phenotype-TAMs, as shown by reduced expression of M2 markers and downregulation of mRNA levels of C-C motif chemokine 22, arginase-1, transforming growth factor-beta 2, and interleukin-10. The study further revealed that CB’s antineoplastic activity involved the downregulation of Wnt5B and β-catenin and upregulation of Axin2, thus inhibiting the Wnt/β-catenin signaling pathway. These findings highlight the therapeutic potential of CB in liver cancer treatment through its modulation of the Wnt/β-catenin pathway and suppression of M2 phenotype-TAM polarization. This study underscores the value of integrating TCM with modern therapeutic strategies to develop novel effective treatments for liver cancer.

Keywords: Calculus bovis; Liver cancer; M2 phenotype tumor-associated macrophages; Wnt/β-catenin pathway; Traditional Chinese medicine; Tumor microenvironment; Antineoplastic therapy

Core Tip: This article discusses the significant findings of Huang et al, who demonstrated that Calculus bovis, a traditional Chinese medicine, exhibits potent anti-liver cancer effects. The study revealed that Calculus bovis effectively inhibits M2 tumor-associated macrophage polarization by modulating the Wnt/β-catenin pathway, leading to reduced tumor growth and improved tumor regression in vivo. These insights underscore the potential of integrating traditional Chinese medicinal approaches with modern therapeutic strategies to develop novel, multi-targeted treatments for liver cancer, addressing a critical need in oncology.