Therapeutic potential of Triptolide in inhibiting breast cancer-induced bone destruction – PTHrP as a therapeutic target

作者：Di Wu, Minghan Li, Huang Zining, Zhou Chunshi, Xiangyu Hu, Wang Zidong, Gang Wu · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1512631 · 被引用次数：2 · 研究领域：Natural Compounds in Disease Treatment、Bone Metabolism and Diseases、Sphingolipid Metabolism and Signaling

Introduction: Bone metastases are a common and severe complication in advanced breast cancer, affecting approximately 65% to 70% of patients and significantly reducing survival time. Osteolytic bone metastases, in particular, are challenging to manage due to their association with skeletal-related events (SREs) that accelerate disease progression and diminish the quality of life. These metastases are driven by a complex interaction between breast cancer cells and the bone microenvironment, leading to increased osteoclast activity and bone destruction. Current treatments, such as bisphosphonates, primarily aim to inhibit osteoclast function but are associated with serious side effects, underscoring the need for alternative therapies. Triptolide (TP), a bioactive compound derived from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F. (TwHF), has demonstrated potent anti-tumor and anti-inflammatory properties, especially in abnormal bone remodeling disorders. This study aims to investigate the therapeutic potential of TP in treating breast cancer-induced bone metastases by examining its effects on osteoclastogenesis and tumor-bone microenvironment interactions. Methods: Mouse bone marrow cells, RAW264.7 pre-osteoclasts and MC3T3-E1 pre-osteoblasts were cultured with MDA-MB-231 breast cancer cells or their conditioned medium to replicate the tumor microenvironment. Osteoclast formation was assessed via TRAP staining. Translational and transcriptional expressio...