Wang Tangyi, Sun Jingwei, Wang Li, Lin Yuxin, Wu Zhijing, Jia Qiangqiang, Zhang Shoude, An Juan, Ma Xueman, Wu Qiong, Su Zhanhai, Wang Haiyan
Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China.
Department of Medical Laboratory, Qinghai Provincial People's Hospital, Xining, Qinghai, China.
Front Immunol. 2025 Mar 5;16:1529710. doi: 10.3389/fimmu.2025.1529710. eCollection 2025.
, a traditional medicinal herb, has garnered significant attention for its potential role in the prevention and treatment of breast cancer. Although clinical recognition of its efficacy has gradually increased, research has shown that contains a variety of chemical components, including triterpenes, carbohydrates, flavonoids, phenolic acids, sesquiterpenes, coumarins, fatty acids, and organic acids. However, the pharmacological mechanisms underlying 's effects and the identification of its key bioactive components warrant further investigation.
Flow cytometry was utilized to investigate the effects of Taraxacum officinale extract (TOE) in combination with PD-1/PD-L1 inhibitor 2 on the immune microenvironment of triple-negative breast cancer (TNBC). Active compounds and their potential targets were identified through an integrative approach involving GeneCards, OMIM, and DisGeNET databases, as well as UPLC-Q-Orbitrap MS analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, followed by molecular docking to explore compound-target interactions. The anti-proliferative effects of isochlorogenic acid A (ICGA-A) and chicoric acid (CRA) on MDA-MB-231 and 4T1 cells were evaluated using the CCK-8 assay. validation was performed using a 4T1 murine model and flow cytometry.
TOE and its active constituents, ICGA-A and CRA, demonstrate potential in augmenting PD-1 blockade therapy for TNBC. This study investigated the combination of ICGA-A and PD-1/PD-L1 inhibitor 2, which significantly enhanced the infiltration of macrophages and CD8+ T cells into tumors in murine models, while concurrently reducing the population of exhausted T cells. Furthermore, CRA notably increased the frequency of CD8+ T cells. Both ICGA-A and CRA therapies were also found to suppress tumor proliferation by inhibiting the FAK/PI3K/AKT/mTOR signaling pathway. These findings highlight the potential of ICGA-A and CRA as effective adjuvants to improve the therapeutic efficacy of PD-1 inhibitor-based immunotherapy in TNBC.
ICGA-A and CRA, bioactive compounds from , exhibit significant antitumor activity in TNBC by targeting the FAK/PI3K/AKT/mTOR pathway, a critical regulator of cancer progression. Their ability to modulate the tumor immune microenvironment highlights their potential as immune modulators that enhance the efficacy of immunotherapy. These findings suggest that ICGA-A and CRA could serve as promising adjuncts in TNBC treatment, offering a novel strategy to overcome challenges such as therapeutic resistance and limited treatment options. Further investigation is warranted to explore their synergistic effects with immunotherapies in improving TNBC outcomes.
蒲公英作为一种传统草药，因其在乳腺癌预防和治疗中的潜在作用而备受关注。尽管其功效在临床上的认可度逐渐提高，但研究表明，蒲公英含有多种化学成分，包括三萜类、碳水化合物、黄酮类、酚酸类、倍半萜类、香豆素类、脂肪酸和有机酸。然而，蒲公英作用的药理机制及其关键生物活性成分的鉴定仍有待进一步研究。
采用流式细胞术研究蒲公英提取物（TOE）与PD-1/PD-L1抑制剂2联合应用对三阴性乳腺癌（TNBC）免疫微环境的影响。通过整合GeneCards、OMIM和DisGeNET数据库以及超高效液相色谱-四极杆-轨道阱质谱分析，鉴定活性化合物及其潜在靶点。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，随后进行分子对接以探索化合物-靶点相互作用。使用CCK-8法评估异绿原酸A（ICGA-A）和菊苣酸（CRA）对MDA-MB-231和4T1细胞的抗增殖作用。使用4T1小鼠模型和流式细胞术进行验证。
TOE及其活性成分ICGA-A和CRA在增强TNBC的PD-1阻断治疗方面显示出潜力。本研究调查了ICGA-A与PD-1/PD-L1抑制剂2的联合应用，结果表明该联合用药显著增强了巨噬细胞和CD8 + T细胞向小鼠模型肿瘤的浸润，同时减少了耗竭T细胞的数量。此外，CRA显著增加了CD8 + T细胞的频率。还发现ICGA-A和CRA疗法均通过抑制FAK/PI3K/AKT/mTOR信号通路来抑制肿瘤增殖。这些发现突出了ICGA-A和CRA作为有效佐剂改善基于PD-1抑制剂的免疫疗法在TNBC中治疗效果的潜力。
ICGA-A和CRA是蒲公英中的生物活性化合物，通过靶向FAK/PI3K/AKT/mTOR通路（癌症进展的关键调节因子）在TNBC中表现出显著的抗肿瘤活性。它们调节肿瘤免疫微环境的能力突出了它们作为免疫调节剂增强免疫治疗效果的潜力。这些发现表明，ICGA-A和CRA有望成为TNBC治疗的辅助药物，为克服治疗耐药性和治疗选择有限等挑战提供了一种新策略。有必要进一步研究以探索它们与免疫疗法在改善TNBC治疗结果方面的协同作用。
