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• W4367672272 endingPage "121735" @default.
• W4367672272 startingPage "121735" @default.
• W4367672272 abstract "Sorafenib (Sora) represents one of the few effective drugs for the treatment of advanced hepatocellular carcinoma (HCC), while resistance and cardiotoxicity limit its therapeutic efficacy. This study investigated the effect of transient receptor potential melastatin 7 (TRPM7) inhibitor, carvacrol (CARV), on overcoming Sora resistance and cardiotoxicity in thioacetamide (TAA) induced HCC in rats. TAA (200 mg/kg/twice weekly, intraperitoneal) was administered for 16 weeks to induce HCC. Rats were treated with Sora (10 mg/Kg/day; orally) and CARV (15 mg/kg/day; orally) alone or in combination, for six weeks after HCC induction. Liver and heart functions, antioxidant capacity, and histopathology were performed. Apoptosis, proliferation, angiogenesis, metastasis, and drug resistance were assessed by quantitative real time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. CARV/Sora combination significantly improved survival rate, and liver functions, reduced Alpha-Fetoprotein level, and attenuated HCC progression compared with Sora group. CARV coadministration almost obviated Sora-induced changes in cardiac and hepatic tissues. The CARV/Sora combination suppressed drug resistance and stemness by downregulating ATP-binding cassette subfamily G member 2, NOTCH1, Spalt like transcription factor 4, and CD133. CARV boosted Sora antiproliferative and apoptotic activities by decreasing cyclin D1 and B-cell leukemia/lymphoma 2 and increasing BCL2-Associated X and caspase-3. CARV/Sora is a promising combination for tumor suppression and overcoming Sora resistance and cardiotoxicity in HCC by modulating TRPM7. To our best knowledge, this study represents the first study to investigate the efficiency of CARV/ Sora on the HCC rat model. Moreover, no previous studies have reported the effect of inhibiting TRPM7 on HCC." @default.
• W4367672272 created "2023-05-03" @default.
• W4367672272 creator A5024952153 @default.
• W4367672272 creator A5036627243 @default.
• W4367672272 creator A5077248134 @default.
• W4367672272 date "2023-07-01" @default.
• W4367672272 modified "2023-09-27" @default.
• W4367672272 title "Carvacrol enhances anti-tumor activity and mitigates cardiotoxicity of sorafenib in thioacetamide-induced hepatocellular carcinoma model through inhibiting TRPM7" @default.
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• W4367672272 doi "https://doi.org/10.1016/j.lfs.2023.121735" @default.
• W4367672272 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37142088" @default.
• W4367672272 hasPublicationYear "2023" @default.

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