Downregulation of Rac1/PAK1/LIMK1/cofilin signaling pathway in colon cancer SW620 cells treated with Chlorin e6 photodynamic therapy

Background: Colorectal cancer is one of the most common gastrointestinal malignancies. Photodynamic therapy (PDT) is a novel and non-invasive treatment for tumors as PDT features small trauma, good applicability, andaccurate targeting. PDT may also be a potential treatment for colon cancer as itmay may induce suppressive effects on metastatic potential.. However, the molecular mechanism of the Chlorin e6 Photodynamic therapy (Ce6-PDT) inhibiting the migration of human colon cancer SW620 cells remains unclear.

Methods: Scratch wound healing assay, scanning electron microscope, MTT, immunofluorescence and laser confocal technique were used to investigate the suppressive effects of Ce6-PDT on the SW620 cells migration, pseudopodia, viability and the actin cytoskeleton. The effect of Ce6-PDT on actin-Filaments and signaling molecules of the Rac1/PAK1/LIMK1/cofilin signaling pathway in SW620 cells were examined by western blot analysis. RNA interference (RNAi) technology was used to establish siRNA-Rac1/SW620 cells. The combined effects of Ce6-PDT and RNAi on colon cancer SW620 cells was investigated by the same technology and methods mentioned above to clarify the signal transduction effect of Rac1/PAK1/LIMK1/cofilin signaling pathway in Ce6-PDT caused inhibition of SW620 cell migration.

Results: The healing and migration rate of the SW620 cells was significantly reduced and the cell pseudopodia were reduced or disappeared by Ce6-PDT. The Immunofluorescence and western blot analysis results showed that Ce6-PDT destroy microfilament's original structure and significantly downregulated F-actin protein expression. The Rac1/PAK1/LIMK1/cofilin signaling pathway was downregulated by Ce6-PDT. Furthermore, the RNAi significantly strengthened the effect of Ce6-PDT on colon cancer SW620 cells migration.

Conclusions: Actin cytoskeleton and protrusions of SW620 cells correlate with its migration ability. Ce6-PDT suppresses SW620 cells migration by downregulating the Rac1/PAK1/LIMK1/cofilin signaling pathway, and its suppressive effect was enhanced by knocking down Rac1 gene expression.