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

Abstract:

BACKGROUND:Colorectal cancer is one of the most common gastrointestinal malignancies. Photodynamic therapy (PDT) is a novel and non-invasive treatment for multiple tumors with its features of small trauma, good applicability, accurate targeting, etc. PDT is also a potential treatment for colon cancer that induces lots of suppressive effects. 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.

authors

Wufuer R,Ma HX,Luo MY,Xu KY,Kang L

doi

10.1016/j.pdpdt.2020.102143

subject

Has Abstract

pub_date

2020-12-08 00:00:00

pages

102143

eissn

1572-1000

issn

1873-1597

pii

S1572-1000(20)30497-X

pub_type

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