Cadmium chloride enhances cisplatin sensitivity in osteosarcoma cells by reducing FOXM1 expression

Oncol Rep. 2020 Aug;44(2):650-660. doi: 10.3892/or.2020.7632. Epub 2020 Jun 4.

Abstract

Osteosarcoma is a highly malignant disease and is associated with a poor patient prognosis and a high mortality rate. Disease prognosis significantly correlates with chemotherapeutic responses. Cadmium is a heavy metal with specific effects on bone, but its benefits for osteosarcoma treatment have not been characterized. In the present study, cadmium chloride was used to treat MG63 osteosarcoma cells, and their gene expression profiles were assessed by GeneChip technology. We found that forkhead box protein M1 (FOXM1) was downregulated by cadmium chloride, and lentiviral‑mediated silencing of FOXM1 confirmed a role for this factor in the cisplatin resistance of MG63 cells. In nude mice, cadmium chloride enhanced the sensitivity of osteosarcoma to cisplatin, an effect mediated by FOXM1. Collectively, these data indicate that cadmium chloride can alter the sensitivity of osteosarcoma cells to cisplatin through FOXM1, highlighting it as a potential therapeutic target and prognostic factor for osteosarcoma.

Keywords: osteosarcoma; cisplatin; cadmium chloride; forkhead box protein M1; drug sensitivity.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Cadmium Chloride / pharmacology*
  • Cadmium Chloride / therapeutic use
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Down-Regulation
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Forkhead Box Protein M1 / genetics
  • Forkhead Box Protein M1 / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Silencing
  • Humans
  • Mice
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • Xenograft Model Antitumor Assays

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Cadmium Chloride
  • Cisplatin