Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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20 (S)-ginsenoside Rh2 inhibits colorectal cancer cell growth by suppressing the Axl signaling pathway in vitro and in vivo

  • Zhang, Haibo (Department of Animal Science and Biotechnology, ITRD, Kyungpook National University) ;
  • Yi, Jun-Koo (Gyeongbuk Livestock Research Institute) ;
  • Huang, Hai (Department of Animal Science and Biotechnology, ITRD, Kyungpook National University) ;
  • Park, Sijun (School of Life Sciences, BK21 FOUR KNU Creative BioResearch, Kyungpook National University) ;
  • Kwon, Wookbong (Division of Biotechnology, DGIST) ;
  • Kim, Eungyung (Department of Animal Science and Biotechnology, ITRD, Kyungpook National University) ;
  • Jang, Soyoung (School of Life Sciences, BK21 FOUR KNU Creative BioResearch, Kyungpook National University) ;
  • Kim, Si-Yong (School of Life Sciences, BK21 FOUR KNU Creative BioResearch, Kyungpook National University) ;
  • Choi, Seong-kyoon (Division of Biotechnology, DGIST) ;
  • Yoon, Duhak (Department of Animal Science and Biotechnology, ITRD, Kyungpook National University) ;
  • Kim, Sung-Hyun (Department of Bio-Medical Analysis, Korea Polytechnic College) ;
  • Liu, Kangdong (China-US (Henan) Hormel Cancer Institute) ;
  • Dong, Zigang (China-US (Henan) Hormel Cancer Institute) ;
  • Ryoo, Zae Young (School of Life Sciences, BK21 FOUR KNU Creative BioResearch, Kyungpook National University) ;
  • Kim, Myoung Ok (Department of Animal Science and Biotechnology, ITRD, Kyungpook National University)
  • Received : 2021.04.03
  • Accepted : 2021.07.17
  • Published : 2022.05.01
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Abstract

Background: Colorectal cancer (CRC) has a high morbidity and mortality worldwide. 20 (S)-ginsenoside Rh2 (G-Rh2) is a natural compound extracted from ginseng, which exhibits anticancer effects in many cancer types. In this study, we demonstrated the effect and underlying molecular mechanism of G-Rh2 in CRC cells in vitro and in vivo. Methods: Cell proliferation, migration, invasion, apoptosis, cell cycle, and western blot assays were performed to evaluate the effect of G-Rh2 on CRC cells. In vitro pull-down assay was used to verify the interaction between G-Rh2 and Axl. Transfection and infection experiments were used to explore the function of Axl in CRC cells. CRC xenograft models were used to further investigate the effect of Axl knockdown and G-Rh2 on tumor growth in vivo. Results: G-Rh2 significantly inhibited proliferation, migration, and invasion, and induced apoptosis and G0/G1 phase cell cycle arrest in CRC cell lines. G-Rh2 directly binds to Axl and inhibits the Axl signaling pathway in CRC cells. Knockdown of Axl suppressed the growth, migration and invasion ability of CRC cells in vitro and xenograft tumor growth in vivo, whereas overexpression of Axl promoted the growth, migration, and invasion ability of CRC cells. Moreover, G-Rh2 significantly suppressed CRC xenograft tumor growth by inhibiting Axl signaling with no obvious toxicity to nude mice. Conclusion: Our results indicate that G-Rh2 exerts anticancer activity in vitro and in vivo by suppressing the Axl signaling pathway. G-Rh2 is a promising candidate for CRC prevention and treatment.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education(2020R1A4A1018280).

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