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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
1Department of Internal Medicine, Jeju National University Hospital, College of Medicine, Jeju National University, Jeju 63241, Republic of Korea.
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.
Insights
Oxaliplatin resistance in colon cancer cells is linked to reduced autophagy. This study found lower autophagy levels and increased reactive oxygen species (ROS) in resistant cells, suggesting a role for ROS in OXT resistance.
Area of Science:
- Cell Biology
- Oncology
- Molecular Medicine
Background:
- Autophagy plays a complex role in cancer, influencing treatment response.
- Oxaliplatin (OXT) is a key chemotherapy agent for colorectal cancer, but resistance is a major clinical challenge.
- The specific mechanisms underlying OXT resistance, particularly the involvement of autophagy, require further elucidation.
Purpose of the Study:
- To investigate and compare the role and levels of autophagy in OXT-sensitive (SNU-C5) versus OXT-resistant (SNU-C5/OXTR) colon cancer cells.
- To explore the relationship between autophagy, reactive oxygen species (ROS) production, and antioxidant pathways in the context of OXT resistance.
- To identify key molecular markers associated with OXT resistance in colon cancer.
Main Methods:
- Comparative analysis of autophagy protein expression (Atg5, beclin-1, Atg7, LC3-I/II, p62) between SNU-C5 and SNU-C5/OXTR cells.
- Assessment of cytotoxicity and apoptosis induction by OXT in both cell lines.
- Measurement of intracellular ROS levels and evaluation of the effect of N-acetylcysteine (ROS scavenger).
- Analysis of antioxidant-related gene expression (Nrf2, HO-1, SOD) in resistant cells.
Main Results:
- SNU-C5/OXTR cells exhibited significantly reduced OXT-induced cytotoxicity and apoptosis compared to SNU-C5 cells.
- Autophagy levels, indicated by lower expression of autophagy proteins (Atg5, beclin-1, Atg7, LC3-I/II) and p62, were significantly decreased in SNU-C5/OXTR cells.
- Intracellular ROS production was markedly higher in SNU-C5/OXTR cells.
- ROS scavenging with N-acetylcysteine partially restored autophagy levels in resistant cells.
- Expression of antioxidant factors (Nrf2, HO-1, SOD) was upregulated in SNU-C5/OXTR cells.
Conclusions:
- Autophagy is significantly downregulated in oxaliplatin-resistant colon cancer cells (SNU-C5/OXTR).
- Increased reactive oxygen species (ROS) production in resistant cells may contribute to the suppression of autophagy.
- These findings suggest a potential link between reduced autophagy, elevated ROS, and the development of oxaliplatin resistance in colon cancer, highlighting potential therapeutic targets.
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