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Reduced Autophagy in 5-Fluorouracil Resistant Colon Cancer Cells

Cheng Wen Yao1, Kyoung Ah Kang1, Mei Jing Piao1

  • 1School of Medicine No.1 and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.

Biomolecules & Therapeutics
|October 15, 2016
PubMed

Insights

Decreased autophagy is linked to 5-fluorouracil (5-FU) resistance in SNUC5 colon cancer cells. Lowered autophagy levels and impaired autophagic flux contribute to this drug resistance.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • 5-fluorouracil (5-FU) is a common chemotherapy drug for colon cancer.
  • Drug resistance, particularly to 5-FU, is a major challenge in colon cancer treatment.
  • Autophagy, a cellular degradation process, plays a complex role in cancer progression and drug response.

Purpose of the Study:

  • To investigate the role of autophagy in the development of 5-fluorouracil (5-FU) resistance in SNUC5 colon cancer cells.
  • To determine if reduced autophagy contributes to 5-FU resistance in this cell line.

Main Methods:

  • Utilized light microscopy, confocal microscopy, and flow cytometry with acridine orange staining to assess autophagy levels.
  • Quantified GFP-LC3 puncta and measured the expression of key autophagy proteins (Atg5, Beclin-1, LC3-II).
  • Assessed autophagic flux and measured reactive oxygen species (ROS) production, including the effect of N-acetyl cysteine (ROS inhibitor).

Main Results:

  • SNUC5/5-FUR cells, resistant to 5-FU, exhibited significantly lower levels of autophagy compared to sensitive cells.
  • Expression of critical autophagic proteins (Atg5, Beclin-1, LC3-II) and autophagic flux were diminished in resistant cells.
  • Elevated reactive oxygen species (ROS) levels were observed in resistant cells, and ROS inhibition further decreased autophagy.

Conclusions:

  • Decreased autophagy is strongly associated with 5-FU resistance in SNUC5 colon cancer cells.
  • Impaired autophagic flux and altered protein expression are characteristic of 5-FU resistant colon cancer cells.
  • The interplay between reduced autophagy and elevated ROS may contribute to 5-FU resistance, suggesting potential therapeutic targets.
Keywords:
5-FluorouracilAutophagyColon cancerReactive oxygen speciesSNUC5/5-FUR

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