2. Academic Validation
  3. FoxG1/BNIP3 axis promotes mitophagy and blunts cisplatin resistance in osteosarcoma

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

  • Cancer Sci. 2024 Jun 26. doi: 10.1111/cas.16242.
Baolong Pan 1,  Yan Li 2,  Huiyun Han 3,  Lu Zhang 4,  Xuemei Hu 1,  Yanyu Pan 5,  Zhuohui Peng 6
Affiliations

Affiliations

  • 1 Health Examination Center, Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunnan, China.
  • 2 Department of Neuroendocrine, Yuxi Children's Hospital, Yuxi, Yunnan, China.
  • 3 Department of Pharmacy, Kunming Children's Hospital, Kunming, Yunnan, China.
  • 4 Department of Asset Management, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • 5 College of Basic Medical Sciences, Naval Medical University, Shanghai, China.
  • 6 Second Department of Orthopedics, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
PMID: 38932521 DOI: 10.1111/cas.16242
Abstract

Cisplatin (CDDP) is a commonly used chemotherapeutic for osteosarcoma (OS) patients, and drug resistance remains as a major hurdle to undermine the treatment outcome. Here, we investigated the potential involvement of FoxG1 and BNIP3 in CDDP resistance of OS cells. FoxG1 and BNIP3 expression levels were detected in the CDDP-sensitive and CDDP-resistant OS tumors and cell lines. Mitophagy was observed through transmission electron microscope analysis. The sensitivity to CDDP in OS cells upon FoxG1 overexpression was examined in cell and animal models. We found that FoxG1 and BNIP3 showed significant downregulation in the CDDP-resistant OS tumor samples and cell lines. CDDP-resistant OS tumor specimens and cells displayed impaired Mitophagy. FoxG1 overexpression promoted BNIP3 expression, enhanced Mitophagy in CDDP-resistant OS cells, and resensitized the resistant cells to CDDP treatment in vitro and in vivo. Our data highlighted the role of the FoxG1/BNIP3 axis in regulating Mitophagy and dictating CDDP resistance in OS cells, suggesting targeting FoxG1/BNIP3-dependent Mitophagy as a potential strategy to overcome CDDP resistance in OS.

Keywords

BNIP3; FoxG1; cisplatin (CDDP); drug resistance; mitophgy; osteosarcoma (OS).

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