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Poncirin downregulates ATP-binding cassette transporters to enhance cisplatin sensitivity in cisplatin-resistant

Liujing Zhao1, Weiwei Zhang2, Fang Zhang1

  • 1Department of Orthopedics, Shanxian Central Hospital, Heze, China.

Phytotherapy Research : PTR
|August 12, 2020
PubMed

Insights

Poncirin, a natural compound, overcomes cisplatin resistance in osteosarcoma cells by reducing drug efflux proteins and inhibiting the PI3K/Akt pathway. This enhances chemotherapy effectiveness and promotes cancer cell death.

Area of Science:

  • Pharmacology
  • Oncology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is a primary bone cancer with limited treatment options.
  • Cisplatin resistance significantly hinders effective OS treatment.
  • Natural compounds offer potential strategies to overcome drug resistance.

Purpose of the Study:

  • To investigate the efficacy of poncirin in overcoming cisplatin resistance in osteosarcoma cells.
  • To elucidate the underlying molecular mechanisms of poncirin's action, focusing on drug resistance pathways.
  • To evaluate poncirin's impact on apoptosis and chemosensitivity.

Main Methods:

  • Cell viability assays (CCK-8) to assess cisplatin sensitivity.
  • Flow cytometry and caspase-3/7 activity assays to measure apoptosis.
  • RT-qPCR and Western blot to analyze the expression of multidrug resistance genes (MDR1, MRP1, BCRP) and the PI3K/Akt pathway.
  • Rescue experiments using a PI3K/Akt activator (740Y-P).

Main Results:

  • Poncirin significantly enhanced cisplatin sensitivity and promoted apoptosis in resistant OS cells.
  • Poncirin downregulated the expression of MDR1, MRP1, and BCRP.
  • Poncirin inhibited the PI3K/Akt signaling pathway, which was crucial for its observed effects.

Conclusions:

  • Poncirin effectively suppresses cisplatin resistance in osteosarcoma by downregulating MDR1, MRP1, and BCRP via PI3K/Akt pathway inhibition.
  • Poncirin represents a promising therapeutic agent for overcoming chemoresistance in osteosarcoma.
  • Targeting the PI3K/Akt pathway in conjunction with poncirin may enhance treatment outcomes.
Keywords:
ABC transporterscisplatin resistanceosteosarcomaponcirinthe PI3K/Akt pathway

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