Department of Surgical ward 2, Wuzhou Traditional Chinese Medicine Hospital, Wuzhou, China.
Biopolymers. 2024 Sep;115(5):e23605. doi: 10.1002/bip.23605. Epub 2024 Jun 12.
Chemotherapy plays a crucial role in the clinical treatment of triple-negative breast cancer (TNBC), but drug resistance limits its clinical application. The active ingredients of Chaihu Shugan Powder (CSP; Bupleurum Liver-Coursing Powder), quercetin and luteolin, both belong to flavonoid compounds and have significant anti-tumor potential, which can promote chemotherapy sensitivity. However, the correlation between the two and TNBC paclitaxel (PTX) chemotherapy sensitivity is unknown. We collected herbal components of CSP from the TCMSP database, and screened effective molecules and corresponding targets. STRING database was utilized to construct a protein-protein interaction network combining effective molecules and target genes. The top 50 nodes ranked by affinity were chosen for subsequent functional analysis, and the drug-active ingredient-gene interaction network was established using Cytoscape software. Molecular docking was used to determine the small molecules that target TNBC PTX resistance. The "clusterProfiler" package was utilized for GO and KEGG enrichment analyses on the top 50 genes to determine the pathways affected by CSP. Cell counting and colony formation assays evaluated cell viability, IC values, and proliferation capacity. Flow cytometry tested PTX intracellular accumulation. Western blot assayed the expression of TNF pathway-related proteins. Active ingredients of CSP, quercetin and luteolin, could inhibit TNBC cell proliferation and promote PTX chemotherapy sensitization. Quercetin and luteolin repressed the TNF signaling pathway and promoted PTX chemotherapy sensitization. Quercetin and luteolin could inhibit TNBC cell proliferation and promote PTX chemotherapy sensitization through the TNF signaling pathway. Therefore, the use of quercetin and luteolin plus PTX treatment provides a prospective strategy for TNBC treatment.
化疗在三阴性乳腺癌（TNBC）的临床治疗中起着至关重要的作用，但耐药性限制了其临床应用。柴胡疏肝散（CSP）的活性成分槲皮素和木樨草素都属于黄酮类化合物，具有显著的抗肿瘤潜力，可以促进化疗敏感性。然而，两者与 TNBC 紫杉醇（PTX）化疗敏感性的相关性尚不清楚。我们从 TCMSP 数据库中收集了 CSP 的草药成分，并筛选出有效分子和相应的靶标。STRING 数据库用于构建一个包含有效分子和靶基因的蛋白质-蛋白质相互作用网络。根据亲和力对前 50 个节点进行排序，用于后续的功能分析，并使用 Cytoscape 软件建立药物-活性成分-基因相互作用网络。分子对接用于确定针对 TNBC PTX 耐药性的小分子。使用“clusterProfiler”软件包对前 50 个基因进行 GO 和 KEGG 富集分析，以确定受 CSP 影响的途径。细胞计数和集落形成试验评估细胞活力、IC 值和增殖能力。流式细胞术检测 PTX 细胞内积累。Western blot 检测 TNF 通路相关蛋白的表达。CSP 的活性成分槲皮素和木樨草素可抑制 TNBC 细胞增殖并促进 PTX 化疗增敏。槲皮素和木樨草素抑制 TNF 信号通路并促进 PTX 化疗增敏。槲皮素和木樨草素可通过 TNF 信号通路抑制 TNBC 细胞增殖并促进 PTX 化疗增敏。因此，使用槲皮素和木樨草素联合 PTX 治疗为 TNBC 治疗提供了一种有前景的策略。
