Synergistic Antiproliferative Effect of Ribociclib (LEE011) and 5-Fluorouracil on Human Colorectal Cancer

Anticancer Res. 2020 Nov;40(11):6265-6271. doi: 10.21873/anticanres.14647.

Abstract

Background/aim: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. This study aimed to investigate the anticancer effect of the combination treatment of Ribociclib (LEE011) and 5-Fluorouracil (5-FU) on CRC cells.

Materials and methods: HT-29 and SW480 cells were treated with LEE011, 5-FU, or the combination of LEE011 and 5-FU. Cell viability and cycle were investigated through 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and flow cytometry. The expression of cell cycle-related proteins was determined through western blot.

Results: The combined treatment of LEE011 with 5-FU synergistically reduced cell viability in HT-29 and SW480 cells. Specifically, it induced cell cycle arrest at the G1 phase, down-regulated the phosphorylation of retinoblastoma protein and the expression of p53.

Conclusion: LEE011 exhibited potential as an effective therapeutic inhibitor for the combination treatment of CRC patients.

Keywords: 5-fluorouracil; Ribociclib; human colorectal cancer.

MeSH terms

  • Aminopyridines / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colorectal Neoplasms / pathology*
  • Drug Synergism
  • Fluorouracil / pharmacology*
  • Humans
  • Purines / pharmacology*

Substances

  • Aminopyridines
  • Cell Cycle Proteins
  • Purines
  • ribociclib
  • Fluorouracil