Cholesterol and steroid synthesis pathways may be involved in the inhibition of osteosarcoma cell viability by calcium-sensing receptor antagonism

The inhibitory effect of NPS-2143 on MG-63 and Saos-2 osteosarcoma tumor cell viability was confirmed. CaSR antagonism significantly up-regulated genes involved in cholesterol and steroid biosynthesis, including <i>CYP51A1</i>, <i>DHCR24</i>, <i>LSS</i>, and <i>MSMO1</i>. These genes encode key enzymes in the cholesterol synthesis pathway, and their upregulation may lead to cholesterol overproduction. This may, in turn, lead to the formation of oxysterols, which are known to induce inflammation and cytotoxicity. These findings suggest a potential metabolic mechanism through which CaSR antagonists influence osteosarcoma cell viability. Although further validation is warranted, our results provide preliminary evidence implicating cholesterol biosynthesis as a mechanistic target in osteosarcoma and underscore the exploratory value of CaSR antagonists as metabolic regulators in cancer research.