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KMID : 0606920220300050447
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Biomolecules & Therapeutics
2022 Volume.30 No. 5 p.447 ~ p.454
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Comparative Study of Autophagy in Oxaliplatin-Sensitive and Resistant SNU-C5 Colon Cancer Cells
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Boo Sun-Jin
Piao Mei Jing
Kang Kyoung-Ah
Zhen Ao Xuan
Fernando Pincha Devage Sameera Madushan
Herath Herath Mudiyanselage Udari Lakmini
Lee Seung-Joo
Song Seung-Eun
Hyun Jin-Won
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Abstract
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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.
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KEYWORD
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Autophagy, Oxaliplatin, Oxaliplatin-resistant SNU-C5 cells, Reactive oxygen species, Colon cancer
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