Chu Tianhao, Ning Yidi, Ma Mingqian, Zhao Zhenying, Liu Jun, Wang Wei, Yu Xueer, Wang Yijia, Zhang Shiwu
Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Nankai University School of Medicine, Nankai University, Tianjin, China.
Cytotechnology. 2025 Feb;77(1):17. doi: 10.1007/s10616-024-00679-2. Epub 2024 Dec 10.
The tumor microenvironment (TME) is important in the recurrence and metastasis of colorectal cancer (CRC). Phillygenin is an effective component of that has long been used in cancer therapy. The mechanism by which phillygenin regulates the TME remains unknown. Methods and Results: A co-culture system of CRC cells and Jurkat T cells was used to simulate the TME . Network pharmacology and Human XL cytokine arrays were used to preliminarily evaluate the role of phillygenin in the TME. The target of phillygenin was determined using transfection of plasmid-producing overexpression of hypoxia-inducible factor 1 alpha (HIF-1α) overexpression or abrogated HIF-1α expression via short hairpin RNA plasmid. The therapeutic effect of phillygenin was assessed in a subcutaneous tumor mouse model. , phillygenin enhanced the immune response of T cells and prevented the immune escape of cancer cells via the inhibition of HIF-1α. Phillygenin upregulated interleukin (IL)-2 and downregulates IL-10 and FOXP3 in Jurkat T cells co-cultured with CRC cells. Phillygenin inhibited expressions of HIF-1α, transforming growth factor-beta, vascular endothelial growth factor, and CD31 in CRC cells cultured alone or with Jurkat T cells. Phillygenin considerably suppressed tumor growth and improved the TME . Conclusions: Phillygenin can enhance the immune response and inhibit angiogenesis in the TME in CRC by inhibiting HIF-1α.
The online version contains supplementary material available at 10.1007/s10616-024-00679-2.
肿瘤微环境（TME）在结直肠癌（CRC）的复发和转移中起重要作用。连翘酯苷是一种长期用于癌症治疗的有效成分。连翘酯苷调节TME的机制尚不清楚。方法和结果：使用CRC细胞和Jurkat T细胞的共培养系统来模拟TME。采用网络药理学和人XL细胞因子阵列初步评估连翘酯苷在TME中的作用。通过转染产生缺氧诱导因子1α（HIF-1α）过表达的质粒或通过短发夹RNA质粒消除HIF-1α表达来确定连翘酯苷的靶点。在皮下肿瘤小鼠模型中评估连翘酯苷的治疗效果。结果表明，连翘酯苷通过抑制HIF-1α增强T细胞的免疫反应并防止癌细胞的免疫逃逸。连翘酯苷上调与CRC细胞共培养的Jurkat T细胞中的白细胞介素（IL）-2，并下调IL-10和FOXP3。连翘酯苷抑制单独培养或与Jurkat T细胞一起培养的CRC细胞中HIF-1α、转化生长因子-β、血管内皮生长因子和CD31的表达。连翘酯苷显著抑制肿瘤生长并改善TME。结论：连翘酯苷可通过抑制HIF-1α增强CRC中TME的免疫反应并抑制血管生成。
在线版本包含可在10.1007/s10616-024-00679-2获取的补充材料。
