Yavuz Halil, Tülüce Yasin, Karakuş Fuat, Köstekci Sedat, Tunçyürekli Merve, Keleş Ahmet Yasin
Department of Biochemistry, Faculty of Veterinary Medicine, Necmettin Erbakan University, 42310, Konya, Türkiye.
Department of Medical Biology, Faculty of Medicine, Van Yüzüncü Yıl University, 65080, Van, Türkiye.
Med Oncol. 2025 Jan 5;42(2):38. doi: 10.1007/s12032-024-02592-2.
The invasion and metastasis of cancer cells transform localized cancers into systemic and life-threatening diseases, posing one of the most significant challenges in cancer treatment. This study tested the hypothesis that combined treatment with Caffeic acid (CA) and metformin (MTF) could inhibit or reduce effective signaling pathways involved in the proliferation, survival, and metastasis of MCF-7 breast cancer cells. Anti-proliferation analysis determined the IC50 values for MTF (4.5 mM) and CA (163 µM) after 72 h. Cell migration analysis showed that MTF and CA significantly inhibited MCF-7 cell migration by the 72nd hour, both alone and in combination, without affecting HME1 healthy cell migration from the 48th hour. Colony formation analysis revealed that CA completely inhibited colony formation in MCF-7 cells, while MTF reduced it by 19%. ELISA results indicated that neither CA nor MTF affected the levels of VEGF-A, E-cadherin, or TINAGL-1 proteins, which are involved in MCF-7 cell migration and invasion. However, MTF significantly reduced IL-1β protein levels, and CA significantly reduced IL-4 protein levels in MCF-7 cells. RT-qPCR results largely supported the ELISA findings. Overall, CA and MTF exhibited potential to inhibit MCF-7 cell apoptosis, migration, tumor microenvironment modulation, and metastasis.
癌细胞的侵袭和转移将局部癌症转变为全身性的、危及生命的疾病，这是癌症治疗中最重大的挑战之一。本研究检验了以下假设：咖啡酸（CA）和二甲双胍（MTF）联合治疗可抑制或减少参与MCF-7乳腺癌细胞增殖、存活和转移的有效信号通路。抗增殖分析确定了72小时后MTF（4.5 mM）和CA（163 µM）的半数抑制浓度（IC50）值。细胞迁移分析表明，MTF和CA在第72小时时单独或联合使用均能显著抑制MCF-7细胞迁移，且从第48小时起不影响HME1健康细胞的迁移。集落形成分析显示，CA完全抑制了MCF-7细胞中的集落形成，而MTF使其减少了19%。酶联免疫吸附测定（ELISA）结果表明，CA和MTF均未影响参与MCF-7细胞迁移和侵袭的血管内皮生长因子A（VEGF-A）、E-钙黏蛋白或肾小管间质相关蛋白1（TINAGL-1）的蛋白水平。然而，MTF显著降低了MCF-7细胞中白细胞介素-1β（IL-1β）的蛋白水平，CA显著降低了IL-4的蛋白水平。逆转录定量聚合酶链反应（RT-qPCR）结果在很大程度上支持了ELISA的结果。总体而言，CA和MTF具有抑制MCF-7细胞凋亡、迁移、肿瘤微环境调节和转移的潜力。
