470 nm LED Irradiation Inhibits the Invasiveness of CD133-positive Human Colorectal Cancer Stem Cells by Suppressing the Cyclooxygenase-2/prostaglandin E2 Pathway

Anticancer Res. 2021 Mar;41(3):1407-1420. doi: 10.21873/anticanres.14898.

Abstract

Background/aim: Recurrence and metastasis of cancer caused by cancer stem cells (CSCs) is a challenge to overcome. Low level laser therapy is a new treatment strategy to suppress their invasiveness. We have assessed the inhibitory effects of 470 nm blue LED on the invasiveness of them to determine the molecular mechanisms of anti-invasiveness.

Materials and methods: The effects of blue LEDs on their viability, proliferation and invasion were analyzed using MTT and transwell methods. In addition, the anti-invasiveness effect of blue LED on them was evaluated by zymography, semi-quantitative RT-PCR and western blot analysis.

Results: Irradiation with blue LED at 3 J/cm2 resulted in inhibition of their viability, proliferation and invasiveness. Their matrix metalloproteinase 2 (MMP-2) and MMP-9 activities were reduced by blue LED irradiation. Semi-quantitative RT-PCR also showed similar results. In addition, western blotting analyses showed that cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis were significantly inhibited by LED irradiation in CD133+ colorectal CSCs.

Conclusion: Down-regulation of the COX-2/PGE2 signaling pathway by blue LED irradiation led to reduce expression of MMP-2 and MMP-9, inhibiting the invasiveness of CD133+ colorectal CSC.

Keywords: 470 nm light emitting diode; Cancer stem cell; colorectal cancer; cyclooxygenase-2/prostaglandin E2 pathway; low level light therapy.

MeSH terms

  • AC133 Antigen / genetics
  • AC133 Antigen / metabolism*
  • Cell Proliferation / genetics
  • Cell Proliferation / radiation effects
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / metabolism*
  • Down-Regulation / radiation effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Lasers, Semiconductor*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / radiation effects*
  • Signal Transduction / radiation effects*
  • Tumor Cells, Cultured

Substances

  • AC133 Antigen
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Dinoprostone