Osthole Increases the Sensitivity of Liver Cancer to Sorafenib by Inhibiting Cholesterol Metabolism.
Osthole is a natural product that has an inhibitory effect on liver cancer, but its effect on the sensitivity of liver cancer to sorafenib is poorly understood. Here, we investigated the effect of osthole and possible sensitization mechanisms. Our results showed that the combination of 2.5 μM sorafe...
| Publicado en: | Nutrition & Cancer Vol. 74; no. 10; pp. 3640 - 3651 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Taylor & Francis Ltd
2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=158962778&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 158962778 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01635581 7MS jtl: Nutrition & Cancer issn: 01635581 maglogo: N pubinfo: dt: 2022 vid: 74 iid: 10 pid: 377 pub: Taylor & Francis Ltd place: Philadelphia, Pennsylvania artinfo: ui: 158962778 157478314 158962778 158962778 10.1080/01635581.2022.2087885 158962778 ppf: 3640 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Osthole Increases the Sensitivity of Liver Cancer to Sorafenib by Inhibiting Cholesterol Metabolism. aug: au: Fan, Ke Huang, Hui Zhao, Ying Xie, Tao Zhu, Zeng-Yan Xie, Mei-Lin affil: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu Province, China sug: subj: Liver Neoplasms Drug Therapy Plants, Medicinal Pharmacodynamics Sorafenib Pharmacodynamics Cholesterol Metabolism Plants, Medicinal Administration and Dosage Sorafenib Administration and Dosage Animal Studies Mice Drug Therapy, Combination Cell Proliferation Colony-Forming Units Assay Cell Migration Inhibition Cell Line, Tumor Tumor Burden Comparative Studies Cholesterol Lipoproteins, LDL Cholesterol Proteins Oxidoreductases ab: Osthole is a natural product that has an inhibitory effect on liver cancer, but its effect on the sensitivity of liver cancer to sorafenib is poorly understood. Here, we investigated the effect of osthole and possible sensitization mechanisms. Our results showed that the combination of 2.5 μM sorafenib and 10 μM osthole had significantly synergistic inhibitory effects on proliferation, colony formation, and migration of HCCLM3, sorafenib-resistant HCCLM3 (HCCLM3-SR), and SK-Hep-1 cells. After treatment of HCCLM3 cells-inoculated subcutaneous xenotransplanted tumor mice with 100 mg/kg osthole, 70 mg/kg sorafenib or their combination for 24 day, the tumor volume, tumor weight, and tumor weight coefficient were significantly lower in the osthole + sorafenib group than in the sorafenib group. Compared with the control group, the total cholesterol and low density lipoprotein-cholesterol contents in serum and tumor tissue were significantly decreased in the osthole or osthole + sorafenib groups, the sterol regulatory element binding protein (SREBP)-2c, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and low-density lipoprotein receptor (LDLR) protein expressions in tumor tissue were significantly downregulated as well. In conclusion, osthole can increase the sensitivity of liver cancer to sorafenib, and the mechanism is related to the downregulations of SREBP-2c, HMGCR, and LDLR protein expressions and subsequent inhibition of cholesterol metabolism. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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