N6-(2-hydroxyethyl)-adenosine (HEA) exhibits antitumor activity for osteosarcoma progression by regulating IGF1 signaling.

BACKGROUND

Osteosarcoma is a highly malignant bone tumor with poor prognosis and limited treatment options due to resistance and side effects.

OBJECTIVES

This study investigates the effects of N6-(2-hydroxyethyl)-adenosine (HEA) on osteosarcoma cells and its impact on the IGF1 signaling pathway.

METHODS

Saos2 and MG63 cell lines were treated with HEA. Cell viability, apoptosis, migration, invasion, and EMT markers were assessed. IGF1 expression was analyzed using Western blot, qPCR, and ELISA. IGF1 silencing and recombinant IGF1 treatments were used to explore HEA's mechanisms.

RESULTS

HEA significantly decreased osteosarcoma cell viability and induced apoptosis in a dose- and time-dependent manner. It also inhibited cell migration and invasion, and modulated EMT markers by upregulating E-cadherin and downregulating N-cadherin and vimentin. HEA downregulated IGF1 at both the mRNA and protein levels, and reduced IGF1 secretion. Furthermore, HEA inhibited the PI3K-AKT signaling pathway, which is activated by IGF1. IGF1 silencing mimicked HEA's effects, whereas recombinant IGF1 pre-treatment partially reversed HEA's effects on cell viability, apoptosis, and EMT markers.

CONCLUSIONS

HEA exerts potent anti-cancer effects on osteosarcoma cells both in vitro and in vivo by targeting the IGF1 pathway and inhibiting downstream PI3K-AKT signaling. These results suggest that HEA holds promise as a novel therapeutic agent for osteosarcoma.