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CD36, a fatty acid receptor, is closely associated with metabolism-related diseases, including cardiovascular disease and cancer. However, the role of CD36 in HFD-accelerated non-small-cell lung cancer (NSCLC) is unclear.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , we fed C57BL\/6J wild-type (WT) and CD36 knockout (CD36\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice normal chow or HFD in the presence or absence of pitavastatin 2\u00a0weeks before subcutaneous injection of LLC1 cells.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , A549 and NCI-H520 cells were treated with free fatty acids (FFAs) to mimic HFD situation for exploration the underlying mechanisms. We found that HFD promoted LLC1 tumor growth\n                    <jats:italic>in vivo<\/jats:italic>\n                    and that FFAs increased cell proliferation and migration in A549 and NCI-H520 cells. The enhanced cell or tumor growth was inhibited by the lipid-lowering agent pitavastatin, which reduced lipid accumulation. More importantly, we found that plasma soluble CD36 (sCD36) levels were higher in NSCLC patients than those in healthy ones. Compared to that in WT mice, the proliferation of LLC1 cells in CD36\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was largely suppressed, which was further repressed by pitavastatin in HFD group. At the molecular level, we found that CD36 inhibition, either with pitavastatin or plasmid, reduced proliferation- and migration-related protein expression through the AKT\/mTOR pathway. Taken together, we demonstrate that inhibition of CD36 expression by pitavastatin or other inhibitors may be a viable strategy for NSCLC treatment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>1) Pitavastatin reduces NSCLC progression by inhibiting CD36.<\/jats:p>\n                  <jats:p>2) Inhibition of\u00a0CD36 can improve HFD- or FFA-induced NSCLC.<\/jats:p>\n                  <jats:p>3) AKT\/mTOR pathway is involved in CD36-regulated NSCLC.<\/jats:p>\n                  <jats:p>4) Inhibition of CD36 by pitavastatin or other inhibitors may be a strategy for NSCLC treatment.<\/jats:p>","DOI":"10.1007\/s10565-024-09848-7","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T02:02:00Z","timestamp":1707184920000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["CD36 inhibition reduces non-small-cell lung cancer development through AKT-mTOR pathway"],"prefix":"10.1007","volume":"40","author":[{"given":"Hui","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peichang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingfeng","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengteng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenzhong","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baotong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahai","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"9848_CR1","doi-asserted-by":"crossref","unstructured":"Bian X, Liu R, Meng Y, Xing D, Xu D, Lu Z. 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