Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2022.028
Comparative Study of Autophagy in Oxaliplatin-Sensitive and Resistant SNU-C5 Colon Cancer Cells
Sun-Jin Boo1,†, Mei Jing Piao2,3,†, Kyoung Ah Kang2,3, Ao Xuan Zhen2, Pincha Devage Sameera Madushan Fernando2, Herath Mudiyanselage Udari Lakmini Herath2, Seung Joo Lee2, Seung Eun Song4 and Jin Won Hyun2,3,*
1Department of Internal Medicine, Jeju National University Hospital, College of Medicine, Jeju National University, Jeju 63241,
2Department of Biochemistry, College of Medicine, Jeju National University, Jeju 63243,
3Jeju Natural Medicine Research Center, Jeju National University, Jeju 63243,
4Department of Anesthesiology, Jeju National University Hospital, College of Medicine, Jeju National University, Jeju 63241, Republic of Korea
*E-mail: jinwonh@jejunu.ac.kr
Tel: +82-64-754-3838, Fax: +82-64-702-2687
The first two authors contributed equally to this work.
Received: February 25, 2022; Revised: April 12, 2022; Accepted: April 13, 2022; Published online: May 25, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 SNUC5/ 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: Autophagy, Oxaliplatin, Oxaliplatin-resistant SNU-C5 cells, Reactive oxygen species, Colon cancer


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