天然产物研究与开发 ›› 2026, Vol. 38 ›› Issue (7): 1526-1535.doi: 10.16333/j.1001-6880.2026.7.015 cstr: 32307.14.1001-6880.2026.7.015

• 开发研究 • 上一篇    下一篇

基于CBX2敲低和EGFR/PI3K通路探讨阿魏酸和顺铂含药血清抑制三阴性乳腺癌侵袭机制

乌日罕1,白  龙1,邢煜舒2*,张慧文2*   

  1. 1内蒙古医科大学蒙医药学院;2内蒙古医科大学药学院,呼和浩特 010010
  • 出版日期:2026-07-24 发布日期:2026-07-23
  • 基金资助:
    内蒙古医科大学中医学(蒙医学)“一流学科”建设项目(myxylxk202303);内蒙古自治区高等学校科学研究项目(NJZY21595);内蒙古自然科学基金(2022MS08025);内蒙古医科大学面上项目(YKD2025MS045)

Mechanism of ferulic acid and cis-diaminodichloroplatinum containing serum inhibiting the invasion of triple-negative breast cancer based on CBX2 knockdown and the EGFR/PI3K pathway

WU Ri-han1,BAI Long1,XING Yu-shu2*,ZHANG Hui-wen2*   

  1. 1College of Mongolian Medicine and Pharmacy,Inner Mongolia Medical University;2College of Pharmacy,Inner Mongolia Medical University,Hohhot 010010,China
  • Online:2026-07-24 Published:2026-07-23

摘要:

探讨阿魏酸(ferulic acid,FA)和顺铂(cis-diaminodichloroplatinum,CDDP)制备的含药血清(FA and CDDP containing serum,FCCS)调节表皮生长因子受体(epidermal growth factor receptor,EGFR)/磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)通路对乳腺癌细胞侵袭、迁移活性的影响。通过制备不同组FCCS,将CBX2敲低和正常的MDA-MB-453和4T1细胞分成对照组(control,Con)、Con+CBX2基因敲低组(Con+CBX2 of short hairpin RNA,Con+shCBX2)、FCCS组、FCCS+shCBX2、FCCS+shCBX2+LY294002(PI3K抑制剂)组、CDDP组。按照以上分组干预48 h后,CCK-8法检测细胞增殖抑制情况;流式细胞术检测对细胞凋亡的影响;Transwell小室检测其对细胞迁移、侵袭能力的影响;ELISA法检测细胞培养上清中上皮钙黏蛋白(E-cadherin)、神经钙黏蛋白(N-cadherin)和血管内皮钙黏蛋白(VE-cadherin)蛋白表达情况;Western blot法检测细胞中磷酸化EGFR(p-EGFR)、磷酸化PI3K(p-PI3K)、E-cadherin和N-cadherin蛋白表达的影响。结果发现,与Con组相比,Con+shCBX2组、FCCS组、FCCS+shCBX2以及FCCS+shCBX2+LY294002组对4T1细胞和MDA-MB-453细胞增殖具有明显抑制作用,FCCS+shCBX2联合LY294002后抑制作用更加显著(均P < 0.05);Annexin V-FITC/PI染色、ELISA和Western blot结果显示,与Con组比较,FCCS组、FCCS+shCBX2以及FCCS+shCBX2+LY294002组细胞凋亡率明显增加(P < 0.05)。EGFR/PI3K转导途径参与了FCCS抑制4T1和MDA-MB-453细胞的增殖、凋亡、侵袭的调控。

关键词: 阿魏酸, 顺铂, 迁移, EGFR/PI3K, 三阴性乳腺癌, CBX2敲低

Abstract:

This study aims to investigate the effects of ferulic acid (FA) and cis-diaminodichloroplatinum (CDDP) containing serum (FCCS) on the invasion and migration of breast cancer cells by regulating the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K) pathway. Different groups of FCCS were prepared, and both CBX2 knockdown and normal MDA-MB-453 and 4T1 cells were divided into the following groups: control (Con), Con+CBX2 of short hairpin RNA (Con+shCBX2), FCCS, FCCS+shCBX2, FCCS+shCBX2+LY294002(PI3K inhibitor), and CDDP. After 48 hours of intervention, cell proliferation inhibition was assessed using the CCK-8 assay; apoptosis was detected by flow cytometry; cell migration and invasion were evaluated using transwell chambers; ELISA was used to measure the expression of E-cadherin, N-cadherin, and VE-cadherin in cell culture supernatants; Western blot was performed to analyze the expression of phosphorylated EGFR (p-EGFR), phosphorylated PI3K (p-PI3K), E-cadherin, and N-cadherin in cells. Compared with Con group, Con+shCBX2, FCCS, FCCS+shCBX2, and FCCS+shCBX2+LY294002 groups significantly inhibited the proliferation of 4T1 and MDA-MB-453 cells, with the strongest inhibition observed in the FCCS+shCBX2+LY294002 group (all P < 0.05). Annexin V-FITC/PI staining, ELISA, and Western blot results showed that, compared with Con group, FCCS, FCCS+shCBX2, and FCCS+shCBX2+LY294002 groups exhibited significantly increased apoptosis rates (P < 0.05). The EGFR/PI3K signaling pathway was involved in FCCS-mediated suppression of proliferation, apoptosis, and invasion in 4T1 and MDA-MB-453 cells.

Key words:

ferulic acid, cis-diaminodichloroplatinum; migration, EGFR/PI3K, triple-negative breast cancer, shCBX2

中图分类号:  R932