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.

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.