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It has been shown that CBD can inhibit the proliferation of ovarian cancer cells, but the underlying specific mechanism is unclear. We previously presented the first evidence for the expression of leukocyte\u2010associated immunoglobulin\u2010like receptor 1 (LAIR\u20101), a member of the immunosuppressive receptor family, in ovarian cancer cells. In the present study, we investigated the mechanism by which CBD inhibits the growth of SKOV3 and CAOV3 ovarian cancer cells, and we sought to understand the concurrent role of LAIR\u20101. In addition to inducing ovarian cancer cell cycle arrest and promoting cell apoptosis, CBD treatment significantly affected the expression of LAIR\u20101 and inhibited the PI3K\/AKT\/mTOR signaling axis and mitochondrial respiration in ovarian cancer cells. These changes were accompanied by an increase in ROS, loss of mitochondrial membrane potential, and suppression of mitochondrial respiration and aerobic glycolysis, thereby inducing abnormal or disturbed metabolism and reducing ATP production. A combined treatment with\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl\u2010\n                    <jats:sc>l<\/jats:sc>\n                    \u2010cysteine and CBD indicated that a reduction in ROS production would restore PI3K\/AKT\/mTOR pathway signaling and ovarian cancer cell proliferation. We subsequently confirmed that the inhibitory effect of CBD on the PI3K\/AKT\/mTOR signal axis and mitochondrial bioenergy metabolism was attenuated by knockdown of LAIR\u20101. Our animal studies further support the in vivo anti\u2010tumor activity of CBD and suggest its mechanism of action. In summary, the present findings confirm that CBD inhibits ovarian cancer cell growth by disrupting the LAIR\u20101\u2010mediated interference with mitochondrial bioenergy metabolism and the PI3K\/AKT\/mTOR pathway. These results provide a new experimental basis for research into ovarian cancer treatment based on targeting LAIR\u20101 with CBD.\n                  <\/jats:p>","DOI":"10.1002\/tox.23752","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T07:21:07Z","timestamp":1677050467000},"page":"1118-1132","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A novel mechanism of cannabidiol in suppressing ovarian cancer through\n                    <scp>LAIR<\/scp>\n                    \u20101 mediated mitochondrial dysfunction and apoptosis"],"prefix":"10.1002","volume":"38","author":[{"given":"Li","family":"Ma","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Binzhou Medical University  Shandong Province China"},{"name":"Fungal Laboratory Jining First People's Hospital  Jining Shandong Province 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