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

Chao He1, Zhenyu Sun1, Robert M Hoffman2,3

  • 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.

Anticancer Research
|April 7, 2019
PubMed
Abstract

Insights

Targeting P-glycoprotein (P-gp) may overcome drug resistance in osteosarcoma (OS). Inhibiting P-gp in OS cells sensitized them to cisplatin, offering a potential strategy to improve patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma (OS) is a primary bone cancer with significant challenges in treatment due to drug resistance and recurrence.
  • Current OS therapies face limitations, necessitating novel strategies to enhance treatment efficacy and patient survival.

Purpose of the Study:

  • To investigate the role of P-glycoprotein (P-gp) in mediating cisplatin resistance in osteosarcoma.
  • To evaluate the potential of P-gp inhibition as a strategy to overcome drug resistance in OS.

Main Methods:

  • Assessed cell viability using CCK-8 and colony formation assays.
  • Analyzed P-gp expression via RT-qPCR and western blot.
  • Utilized a xenograft mouse model to test the synergistic effect of a P-gp inhibitor with cisplatin.

Main Results:

  • P-gp expression levels correlated with cisplatin resistance in OS patients.
  • Osteosarcoma cells with high P-gp expression exhibited increased resistance to cisplatin.
  • Knockdown or inhibition of P-gp significantly sensitized OS cells to cisplatin treatment.

Conclusions:

  • Down-regulating P-gp expression presents a promising therapeutic strategy for overcoming cisplatin resistance in osteosarcoma.
  • Targeting P-gp may improve the efficacy of chemotherapy in OS patients.
Keywords:
OsteosarcomaP-Glycoproteincisplatin resistance

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