Anti-ENO1 antibody combined with metformin against tumor resistance: a novel antibody-based platform

• Published in: PeerJ (San Francisco, CA) CA), 2024-03, Vol.12, p.e16817-e16817, Article e16817
• Main Authors: Shu, Xiong, Zhang, Hui Wen, Liu, Shi Ya, Sun, Li Xin, Zhang, Tao, Ran, Yu Liang
• Format: Article
• Language: English
• Subjects: Antibody-based drug combination therapy; beta Catenin - metabolism; Biochemistry; Cancer stem cells; Cell Biology; Cell Line, Tumor; Cetuximab; Cisplatin - pharmacology; Drug resistance; ENO1; Metformin - pharmacology; Molecular Biology; Oncology; Oncotherapy; Pharmacology; Phosphatidylinositol 3-Kinases - metabolism
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.16817

Antibody-based platforms ( , ADC) have emerged as one of the most encouraging tools for the cancer resistance caused by cancer stem cells (CSCs) enrichment. Our study might provide a promising therapeutic direction against drug resistance and serve as a potential precursor platform for screening ADC. The cell migration, invasion, drug resistance, and self-renewal were assessed by the cell invasion and migration assay, wound healing assay, CCK-8 assay, colony formation assay, and sphere formation assay, respectively. The expression profiles of CSCs (ALDH and CD44 ) subpopulations were screened by flow cytometry. The western blot and cell immunofluorescence assay were used to evaluate pathway-related protein expression in both anti-ENO1 antibody, MET combined with DPP/CTX-treated CSCs. In the present study, western blot and flow cytometry verified that anti-ENO1 antibody target the CD44 subpopulation by inhibiting the PI3K/AKT pathway, while metformin might target the ALDH subpopulation through activation of the AMPK pathway and thus reverse drug resistance to varying degrees. Subsequently, investigation indicated that anti-ENO1 antibody, metformin combined with cisplatin/cetuximab could simultaneously target ALDH and CD44 subpopulations. The combination also inhibited the CSCs proliferation, migration, invasion, and sphere formation; which may result in overcoming the drug resistance. Then, molecular mechanism exploration verified that the anti-ENO1 antibody, metformin combined with cisplatin/cetuximab inhibited the Wnt/β-catenin signaling. The study preliminarily revealed anti-ENO1 antibody combined with metformin could overcome drug resistance against CSCs by inhibiting the Wnt//β-catenin pathway and might serve as a potential precursor platform for screening ADC. More importantly, it is reasonably believed that antibody-based drug combination therapy might function as an encouraging tool for oncotherapy.