Adipocytes Promote Cisplatin Resistance through Secreting A1BG and Regulating NAMPT/PARP1 Axis-Mediated DNA Repair in Osteosarcoma.

ABSTRACT: Obesity is increasingly recognized as a negative prognostic factor for cancers, including osteosarcoma. However, the mechanisms linking obesity to chemoresistance in osteosarcoma remain unclear. This study found obesity is significantly associated with poor responses to cisplatin-based chemotherapy in osteosarcoma patients. In vitro, adipocyte-conditioned medium (Adi-CM) induced cisplatin resistance, while peritumoral adipocytes and diet-induced obesity (DIO) reduce the cisplatin efficacy in vivo. Mechanistically, Adi-CM enhanced DNA repair by the PARP1/ATM pathway activation. Proteomic analysis identified A1BG, a secreted protein upregulated in adipocytes from chemoresistant patients, as a key mediator of this effect. A1BG depletion in adipocytes restored cisplatin sensitivity, whereas re

SUBMITTER: Liang Y 

PROVIDER: S-EPMC12463075 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature