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Norcantharidin potentiates sorafenib antitumor activity in hepatocellular carcinoma rat model through inhibiting IL-6/STAT3 pathway.
Yousef, Eman H; El-Magd, Nada F Abo; El Gayar, Amal M.
Afiliação
  • Yousef EH; Biochemistry department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Biochemistry department, Faculty of Pharmacy, Horus University-Egypt, Damietta, Egypt. Electronic address: ehamdy@horus.edu.eg.
  • El-Magd NFA; Biochemistry department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
  • El Gayar AM; Biochemistry department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. Electronic address: elgayaramal@gmail.com.
Transl Res ; 260: 69-82, 2023 10.
Article em En | MEDLINE | ID: mdl-37257560
ABSTRACT
In hepatocellular carcinoma (HCC), sorafenib (Sora) efficacy is limited by primary and/or acquired resistance. Emerging evidence shows that the inflammatory factor interleukin 6 (IL-6) plays a role in Sora resistance. Norcantharidin (NCTD), a derivative of cantharidine, was identified as a potent IL-6 inhibitor. Thus, in this study, we evaluated NCTD ability to improve the Sora efficacy in HCC and its underlying molecular mechanisms. Male Sprague Dawely rats were administered NCTD (0.1 mg/kg/day; orally) or Sora (10 mg/kg day; orally) or combination for 6 weeks after HCC induction using thioacetamide (200 mg/kg; ip; 2 times/wk) for 16 weeks. Our results showed that NCTD greatly enhanced Sora activity against HCC and potentiated Sora-induced oxidative stress. NCTD enhanced Sora-induced tumor immunity reactivation by decreasing both fibrinogen-like protein 1 level and increasing both tumor necrosis factorgene expression along with CD8+ T cells number. Also, NCTD augmented Sora attenuation activity against TAA-induced angiogenesis and metastasis by decreasing VEGFA, HIF-1α, serum lactate dehydrogenase enzyme, and vimentin levels. The combined use of NCTD/Sora suppressed drug resistance and stemness by downregulating ATP-binding cassette subfamily G member 2, neurogenic locus notch homolog protein, spalt-like transcription factor 4, and CD133. NCTD boosted Sora antiproliferative and apoptotic activities by decreasing Ccnd1 and BCL2 expressions along with increasing BAX and caspase-3 expressions. To our knowledge, this study represents the first study providing evidence for the potential novel therapeutic use of NCTD/Sora combination for HCC. Moreover, no previous studies have reported the effect of NCTD on FGL1.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas / Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas / Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article