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FoxG1/BNIP3 axis promotes mitophagy and blunts cisplatin resistance in osteosarcoma

Baolong Pan1, Yan Li2, Huiyun Han3

  • 1Health Examination Center, Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunnan, China.

Cancer Science
|June 27, 2024
PubMed

Insights

Drug resistance to cisplatin chemotherapy in osteosarcoma is a major challenge. This study reveals that restoring FoxG1 and BNIP3 expression can enhance mitophagy and resensitize osteosarcoma cells to cisplatin treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cisplatin (CDDP) is a cornerstone chemotherapy for osteosarcoma (OS).
  • Drug resistance to CDDP significantly limits treatment efficacy in OS patients.
  • Understanding the mechanisms of CDDP resistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the roles of FoxG1 and BNIP3 in CDDP resistance in osteosarcoma.
  • To explore the potential of targeting the FoxG1/BNIP3 axis to overcome CDDP resistance.

Main Methods:

  • Assessed FoxG1 and BNIP3 expression in CDDP-sensitive and resistant OS tumors and cell lines.
  • Utilized transmission electron microscopy to observe mitophagy.
  • Examined CDDP sensitivity in OS cells with FoxG1 overexpression using in vitro and in vivo models.

Main Results:

  • FoxG1 and BNIP3 were significantly downregulated in CDDP-resistant OS samples and cells.
  • CDDP-resistant OS cells exhibited impaired mitophagy.
  • Overexpression of FoxG1 upregulated BNIP3, enhanced mitophagy, and restored CDDP sensitivity in resistant OS cells.

Conclusions:

  • The FoxG1/BNIP3 axis plays a critical role in regulating mitophagy and CDDP resistance in osteosarcoma.
  • Targeting FoxG1/BNIP3-dependent mitophagy presents a promising strategy to overcome CDDP resistance in OS treatment.
Keywords:
BNIP3FoxG1cisplatin (CDDP)drug resistancemitophgyosteosarcoma (OS)

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