{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:56:54Z","timestamp":1771549014554,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Universities","award":["2572022DQ06"],"award-info":[{"award-number":["2572022DQ06"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["82273107"],"award-info":[{"award-number":["82273107"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["81872293"],"award-info":[{"award-number":["81872293"]}]},{"name":"National Natural Science Foundation of China","award":["2572022DQ06"],"award-info":[{"award-number":["2572022DQ06"]}]},{"name":"National Natural Science Foundation of China","award":["82273107"],"award-info":[{"award-number":["82273107"]}]},{"name":"National Natural Science Foundation of China","award":["81872293"],"award-info":[{"award-number":["81872293"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Polydatin (PD) is a natural compound with anticancer activities, but the underlying mechanisms remain largely unclear. To understand how PD inhibited hepatocellular carcinoma (HCC), we studied PD treatments in HCC HepG2 and SK-HEP1 cells, and normal liver HL-7702 cells. PD selectively blocked the proliferation of HCC cells but showed low toxicity in normal cells, while the effects of doxorubicin (DOX) and cisplatin (DDP) on HCC and normal liver cells were opposite. In the cotreatment studies, PD synergistically improved the inhibitory activities of DOX and DDP in HCC cells but alleviated their toxicity in HL-7702 cells. Furthermore, RNA-seq studies of PD-treated HepG2 cells revealed multiple altered signaling pathways. We identified 1679 Differentially Expressed Genes (DEGs) with over a 2.0-fold change in response to PD treatment. Integrative analyses using the DEGs in PD-treated HepG2 cells and DEGs in a TCGA dataset of HCC patients revealed five PD-repressed DEGs regulating mitotic spindle midzone formation. The expression of these genes showed significantly positive correlation with poor clinical outcomes of HCC patients, suggesting that mitotic machinery was likely a primary target of PD. Our findings improve the understanding of PD\u2019s anticancer mechanisms and provide insights into developing effective clinical approaches in HCC therapies.<\/jats:p>","DOI":"10.3390\/cells12020222","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:33:30Z","timestamp":1672882410000},"page":"222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Polydatin Inhibits Hepatocellular Carcinoma Cell Proliferation and Sensitizes Doxorubicin and Cisplatin through Targeting Cell Mitotic Machinery"],"prefix":"10.3390","volume":"12","author":[{"given":"Umar","family":"Farooq","sequence":"first","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingru","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyue","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shah","family":"Jehan","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinming","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dangdang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-5585","authenticated-orcid":false,"given":"Guangchao","family":"Sui","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S1535-6108(04)00058-3","article-title":"Focus on hepatocellular carcinoma","volume":"5","author":"Bruix","year":"2004","journal-title":"Cancer Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/13645706.2018.1432489","article-title":"Transvascular therapy of Hepatocellular Carcinoma (HCC), status and developments","volume":"27","author":"Gnutzmann","year":"2018","journal-title":"Minim. 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