{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:19:02Z","timestamp":1791433142837,"version":"4.3.3"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The cannabinoid receptor 2 (CB2) is mainly involved in the immune system. However, although CB2 has been reported to play an anti\u2010tumor function in breast cancer (BC), its specific mechanism in BC remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined the expression and prognostic significance of CB2 in BC tissues by qPCR, second\u2010generation sequencing, western blot, and immunohistochemistry. We assessed the impacts of overexpression and a specific agonist of CB2 on the growth, proliferation, apoptosis, and drug resistance of BC cells in vitro and in vivo using CCK\u20108, flow cytometry, TUNEL staining, immunofluorescence, tumor xenografts, western blot, and colony formation assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CB2 expression was significantly lower in BC compared with paracancerous tissues. It was also highly expressed in benign tumors and ductal carcinoma in situ, and its expression was correlated with prognosis in BC patients. CB2 overexpression and treatment of BC cells with a CB2 agonist inhibited proliferation and promoted apoptosis, and these actions were achieved by suppressing the PI3K\/Akt\/mTOR signaling pathway. Moreover, CB2 expression was increased in MDA\u2010MB\u2010231 cell treated with cisplatin, doxorubicin, and docetaxel, and sensitivity to these anti\u2010tumor drugs was increased in BC cells overexpressing CB2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings reveal that CB2 mediates BC via the PI3K\/Akt\/mTOR signaling pathway. CB2 could be a novel target for the diagnosis and treatment of BC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6037","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T18:30:17Z","timestamp":1684866617000},"page":"13538-13550","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Overexpression of cannabinoid receptor 2 is associated with human breast cancer proliferation, apoptosis, chemosensitivity and prognosis via the PI3K\/Akt\/mTOR signaling pathway"],"prefix":"10.1002","volume":"12","author":[{"given":"Qiang","family":"Song","sequence":"first","affiliation":[{"name":"Department of Central Laboratory Chongqing University Three Gorges Hospital Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory Chongqing University Three Gorges Hospital Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chongqing University Three Gorges Hospital Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Chongqing University Three Gorges Hospital, Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiurong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory Chongqing University Three Gorges Hospital Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Chongqing University Three Gorges Hospital, Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Chongqing University Three Gorges Hospital, Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory Chongqing University Three Gorges Hospital Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory Chongqing University Three Gorges Hospital Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7951-9002","authenticated-orcid":false,"given":"Xiaohe","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory Chongqing University Three Gorges Hospital Chongqing University  Wanzhou, Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2016.17.S3.43"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33588"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00279-5"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.5603\/GP.2016.0062"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soc.2017.01.013"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suronc.2015.06.007"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063545"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030525"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-015-9608-y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0602-547"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986711795471374"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2016.1177512"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv077"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-021-04158-6"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109080"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605248"},{"key":"e_1_2_10_18_1","first-page":"5784","article-title":"Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor","volume":"61","author":"Sanchez C","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.03.003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2018.09.006"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-8716(99)00152-0"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(00)00161-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2016.268953"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9408"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106535"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2019.11.006"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105302"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.204"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-21737-2_4"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26133866"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00416-0"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.02.027"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.12.008"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124507"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.05.012"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.08.016"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22917"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092188"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-06-0004"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-019-04958-6"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21700"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2006.08.001"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.56173"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165788"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-016-0744-y"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8090957"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-20-0771"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.6037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:05:04Z","timestamp":1699362304000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.6037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/cam4.6037"],"URL":"https:\/\/doi.org\/10.1002\/cam4.6037","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]},"assertion":[{"value":"2022-07-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}