Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Comparative Study of Autophagy in Oxaliplatin-Sensitive and Resistant SNU-C5 Colon Cancer Cells

  • Boo, Sun-Jin (Department of Internal Medicine, Jeju National University Hospital, College of Medicine, Jeju National University) ;
  • Piao, Mei Jing (Department of Biochemistry, College of Medicine, Jeju National University) ;
  • Kang, Kyoung Ah (Department of Biochemistry, College of Medicine, Jeju National University) ;
  • Zhen, Ao Xuan (Department of Biochemistry, College of Medicine, Jeju National University) ;
  • Fernando, Pincha Devage Sameera Madushan (Department of Biochemistry, College of Medicine, Jeju National University) ;
  • Herath, Herath Mudiyanselage Udari Lakmini (Department of Biochemistry, College of Medicine, Jeju National University) ;
  • Lee, Seung Joo (Department of Biochemistry, College of Medicine, Jeju National University) ;
  • Song, Seung Eun (Department of Anesthesiology, Jeju National University Hospital, College of Medicine, Jeju National University) ;
  • Hyun, Jin Won (Department of Biochemistry, College of Medicine, Jeju National University)
  • Received : 2022.02.25
  • Accepted : 2022.04.13
  • Published : 2022.09.01
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Abstract

Few studies have evaluated the role of autophagy in the development of oxaliplatin (OXT) resistance in colon cancer cells. In this study, we compared the role of autophagy between SNU-C5 colon cancer cells and OXT-resistant SNU-C5 (SNU-C5/OXTR) cells. At the same concentration of OXT, the cytotoxicity of OXT or apoptosis was significantly reduced in SNU-C5/OXTR cells compared with that in SNU-C5 cells. Compared with SNU-C5 cells, SNU-C5/OXTR cells exhibited low levels of autophagy. The expression level of important autophagy proteins, such as autophagy-related protein 5 (Atg5), beclin-1, Atg7, microtubule-associated proteins 1A/1B light chain 3B I (LC3-I), and LC3-II, was significantly lower in SNU-C5/OXTR cells than that in SNU-C5 cells. The expression level of the autophagy-essential protein p62 was also lower in SNU-C5/OXTR cells than in SNU-C5 cells. In SNU-C5/OXTR cells, the production of intracellular reactive oxygen species (ROS) was significantly higher than that in SNU-C5 cells, and treatment with the ROS scavenger N-acetylcysteine restored the reduced autophagy levels. Furthermore, the expression of antioxidant-related nuclear factor erythroid 2-related factor 2 transcription factor, heme oxygenase-1, and Cu/Zn superoxide dismutase were also significantly increased in SNU-C5/OXTR cells. These findings suggest that autophagy is significantly reduced in SNU-C5/OXTR cells compared with SNU-C5 cells, which may be related to the production of ROS in OXT-resistant cells.

Keywords

Acknowledgement

This work was supported by a research grant from Jeju National University Hospital in 2020.

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