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

Xiong Shu1, Hui Wen Zhang2, Shi Ya Liu2

  • 1National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing JiShuiTan Hospital, Beijing, China.

Peerj
|March 22, 2024
PubMed
Abstract

Insights

Antibody-drug conjugates (ADCs) show promise against cancer stem cells (CSCs). This study found that combining an anti-ENO1 antibody with metformin can overcome drug resistance by inhibiting the Wnt/β-catenin pathway.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Cancer stem cells (CSCs) enrichment contributes to cancer drug resistance.
  • Antibody-based drug conjugates (ADCs) are promising therapeutic tools against CSCs.
  • Developing novel strategies to overcome CSC-mediated drug resistance is crucial for effective cancer therapy.

Purpose of the Study:

  • To investigate the efficacy of an anti-ENO1 antibody combined with metformin in overcoming CSC-mediated drug resistance.
  • To explore the underlying molecular mechanisms of this combination therapy.
  • To evaluate the potential of this combination as a precursor platform for screening ADCs.

Main Methods:

  • Flow cytometry to analyze CSC subpopulations (ALDH+, CD44+).
  • Cell-based assays (migration, invasion, CCK-8, colony formation, sphere formation) to assess CSC functions.
  • Western blot and immunofluorescence to evaluate protein expression and pathway activation (PI3K/AKT, AMPK, Wnt/β-catenin).

Main Results:

  • The anti-ENO1 antibody targets CD44+ CSCs via PI3K/AKT inhibition, while metformin targets ALDH+ CSCs via AMPK activation.
  • The combination therapy simultaneously targets both CSC subpopulations, inhibiting proliferation, migration, invasion, and sphere formation.
  • Molecular analysis revealed that the combination therapy inhibits the Wnt/β-catenin signaling pathway, thereby overcoming drug resistance.

Conclusions:

  • The combination of anti-ENO1 antibody and metformin effectively overcomes drug resistance in CSCs by inhibiting the Wnt/β-catenin pathway.
  • This combination therapy shows potential as a precursor platform for screening antibody-drug conjugates (ADCs).
  • Antibody-based combination therapies represent a promising strategy for oncotherapy.
Keywords:
Antibody-based drug combination therapyCancer stem cellsDrug resistanceENO1Oncotherapy

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