P-Glycoprotein Overexpression Is Associated With Cisplatin Resistance in Human Osteosarcoma

Anticancer Res. 2019 Apr;39(4):1711-1718. doi: 10.21873/anticanres.13277.

Abstract

Background/aim: Osteosarcoma (OS) is a diagnosed primary cancer of the bone. Despite the great advances that have been made during the past decades in OS therapy, drug resistance and tumor recurrence are still major problems. It is urgent to find novel strategies to overcome drug resistance in order to prolong the survival time of OS patients.

Materials and methods: Cell viability was investigated by the cell count kit-8 (CCK-8) and colony formation assays. P-Glycoprotein (P-gp) expression was analyzed by RT-qPCR and western blot. A xenograft mouse model was used to identify the synergistic efficacy of a P-gp inhibitor with cisplatin. Student's t-test was used to determine statistically significant differences.

Results: P-gp expression levels were associated with cisplatin efficacy in OS patients. OS cells with higher P-gp expression were more resistant to cisplatin. Knockdown or inhibition of P-gp sensitized OS cells to cisplatin.

Conclusion: Down-regulating the expression of P-gp in OS maybe a promising strategy to overcome cisplatin resistance.

Keywords: Osteosarcoma; P-Glycoprotein; cisplatin resistance.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Nude
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Time Factors
  • Tumor Burden / drug effects
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • Cisplatin