Morpholino-driven blockade of Dkk-1 in osteosarcoma inhibits bone damage and tumour expansion by multiple mechanisms.

ABSTRACT:

Background

Osteosarcoma (OS) is the most common primary bone malignancy. Chemotherapy plays an essential role in OS treatment, potentially doubling 5-year event-free survival if tumour necrosis can be stimulated. The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) enhances OS survival in part through upregulation of aldehyde-dehydrogenase-1A1 which neutralises reactive oxygen species originating from nutritional stress and chemotherapeutic challenge.

Methods

A vivo morpholino (DkkMo) was employed to block the expression of Dkk-1 in OS cells. Cell mitosis, gene expression and bone destruction were measured in vitro and in vivo in the presence and absence of doxorubicin (DRB).

Results

DkkMo reduced the expression of Dkk-1 and Aldh1a1, reduced expansion of OS tumours, preserv

SUBMITTER: Pan S 

PROVIDER: S-EPMC9276700 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature