BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Synergistic antitumor activity of sorafenib and MG149 in hepatocellular carcinoma cells

  • Moon, Byul (Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST)) ;
  • Park, Mijin (Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST)) ;
  • Cho, Seung-Hyun (Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST)) ;
  • Kim, Kang Mo (Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Seo, Haeng Ran (Advanced Biomedical Research Laboratory, Institut Pasteur Korea) ;
  • Kim, Jeong-Hoon (Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST)) ;
  • Kim, Jung-Ae (Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST))
  • 투고 : 2022.02.23
  • 심사 : 2022.06.09
  • 발행 : 2022.10.31
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초록

Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress.

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과제정보

This work was supported by a grant (NRF-2019R1A2C10861 5114 to J.-A.K.) from the National Research Foundation, Ministry of Science and ICT, and by the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (171134054 to J.-A.K. and 1711170633 to J.-H.K and J.-A.K.).

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