Wnt/β-catenin signaling pathway activation reverses gemcitabine resistance by attenuating Beclin1-mediated autophagy in the MG63 human osteosarcoma cell line

Mol Med Rep. 2017 Aug;16(2):1701-1706. doi: 10.3892/mmr.2017.6828. Epub 2017 Jun 21.

Abstract

Anaberrant Wnt/β-catenin signaling pathway is frequently implicated in tumorigenesis. However, whether the Wnt/β‑catenin pathway plays a role in resistance to antitumor chemotherapy drugs remains unknown. In the present study, the process of autophagy was assessed following overexpression of the autophagy‑associated gene Beclin 1 in gemcitabine‑induced MG63 human osteosarcoma cells. Autophagy‑associated gene expression was measured following activation or inhibition of the Wnt/β‑catenin pathway in gemcitabine‑induced MG63 cells using reverse transcription‑quantitative polymerase chain reaction. In addition, the percentage of MG63 cell apoptosis was measured by flow cytometry following Wnt/β‑catenin pathway activation or inhibition. The results demonstrated that Beclin 1 overexpression induced autophagy and reduced gemcitabine‑induced apoptosis in MG63 human cell line. Furthermore, activation of the Wnt/β‑catenin signaling pathway attenuated autophagy and enhanced gemcitabine‑induced apoptosis. Additionally, the expression of Beclin 1 was reduced following Wnt/β‑catenin signaling pathway activation. The present study demonstrated that activation of the Wnt/β‑catenin signaling pathway may rescue chemotherapy drug resistance by downregulating the expression of Beclin 1.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Beclin-1 / genetics
  • Beclin-1 / metabolism*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 7 / genetics
  • Caspase 7 / metabolism
  • Cell Line, Tumor
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Gemcitabine
  • Genes, bcl-2
  • Humans
  • Lysosomal Membrane Proteins / genetics
  • Lysosomal Membrane Proteins / metabolism
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Wnt Signaling Pathway / drug effects*

Substances

  • Antineoplastic Agents
  • Autophagy-Related Proteins
  • BECN1 protein, human
  • Beclin-1
  • CCND1 protein, human
  • LAMP1 protein, human
  • Lysosomal Membrane Proteins
  • Deoxycytidine
  • Cyclin D1
  • Caspase 3
  • Caspase 7
  • Gemcitabine