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SOD1 inhibition enhances sorafenib efficacy in HBV-related hepatocellular carcinoma by modulating PI3K/Akt/mTOR pathway and ROS-mediated cell death.
Lee, Jooyoung; Kim, Jiye; Lee, Ryunjin; Lee, Eunkyeong; An, Hye-In; Kwon, Yong-Jae; Jin, Hana; Pack, Chan-Gi; Kim, Inki; Yoon, Young-In; Park, Gil-Chun; Jwa, Eun-Kyoung; Kwon, Jae Hyun; Namgoong, Jung-Man; Song, Gi-Won; Hwang, Shin; Tak, Eunyoung; Lee, Sung-Gyu.
Afiliação
  • Lee J; Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Kim J; Department of Biochemistry and Molecular Biology, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Lee R; Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Lee E; Department of Biochemistry and Molecular Biology, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • An HI; Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Kwon YJ; Department of Biochemistry and Molecular Biology, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Jin H; Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Pack CG; Department of Biochemistry and Molecular Biology, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Kim I; Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Yoon YI; Department of Biochemistry and Molecular Biology, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Park GC; Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Seoul, South Korea.
  • Jwa EK; Division of Vascular Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Kwon JH; Convergence Medicine Research Center (CREDIT), Asan Institute for Life Sciences, ASAN Medical Center, Seoul, Republic of Korea.
  • Namgoong JM; Convergence Medicine Research Center (CREDIT), Asan Institute for Life Sciences, ASAN Medical Center, Seoul, Republic of Korea.
  • Song GW; Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Hwang S; Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Tak E; Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Lee SG; Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
J Cell Mol Med ; 28(14): e18533, 2024 Jul.
Article em En | MEDLINE | ID: mdl-39034442
ABSTRACT
Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Vírus da Hepatite B / Espécies Reativas de Oxigênio / Carcinoma Hepatocelular / Fosfatidilinositol 3-Quinases / Proteínas Proto-Oncogênicas c-akt / Serina-Treonina Quinases TOR / Superóxido Dismutase-1 / Sorafenibe / Neoplasias Hepáticas Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Vírus da Hepatite B / Espécies Reativas de Oxigênio / Carcinoma Hepatocelular / Fosfatidilinositol 3-Quinases / Proteínas Proto-Oncogênicas c-akt / Serina-Treonina Quinases TOR / Superóxido Dismutase-1 / Sorafenibe / Neoplasias Hepáticas Idioma: En Ano de publicação: 2024 Tipo de documento: Article